TY  - JOUR
AU  - Martinović, Jelena
AU  - Samardžić, Janko
AU  - Zarić Kontić, Marina
AU  - Ivković, Sanja
AU  - Dacić, Sanja
AU  - Major, Tamara
AU  - Radosavljević, Milica
AU  - Svob Strac, Dubravka
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12975
AB  - Zaleplon is a positive allosteric modulator of the γ-aminobutyric acid (GABA)A receptor approved for the short-term treatment of insomnia. Previous publications on zaleplon have not addressed the proteins involved in its mechanism of action but have mostly referred to behavioral or pharmacological studies. Since both GABAergic and glutamatergic signaling have been shown to regulate wakefulness and sleep, we examined the effects of prolonged zaleplon treatment (0.625 mg/kg for 5 days) on these systems in the hippocampus of male Wistar rats. Western blot and immunohistochemical analyses showed that the upregulated components of GABAergic signaling (glutamate decarboxylase, vesicular GABA transporter, GABA, and α1 subunit of the GABAA receptor) were accompanied by increased protein levels in the glutamatergic system (vesicular glutamate transporter 1 and NR1, NR2A, and NR2B subunits of N-methyl-d-aspartate receptor). Our results, showing that zaleplon enhances GABA neurotransmission in the hippocampus, were not surprising. However, we found that treatment also increased glutamatergic signaling. This could be the result of the downregulation of adenosine A1 receptors, important modulators of the glutamatergic system. Further studies are needed to investigate the effects of the zaleplon-induced increase in hippocampal glutamatergic neurotransmission and the possible involvement of the adenosine system in zaleplon’s mechanism of action.
T2  - Brain Sciences
T1  - Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus
VL  - 13
IS  - 12
SP  - 1707
DO  - 10.3390/brainsci13121707
ER  - 

@article{
author = "Martinović, Jelena and Samardžić, Janko and Zarić Kontić, Marina and Ivković, Sanja and Dacić, Sanja and Major, Tamara and Radosavljević, Milica and Svob Strac, Dubravka",
year = "2023",
abstract = "Zaleplon is a positive allosteric modulator of the γ-aminobutyric acid (GABA)A receptor approved for the short-term treatment of insomnia. Previous publications on zaleplon have not addressed the proteins involved in its mechanism of action but have mostly referred to behavioral or pharmacological studies. Since both GABAergic and glutamatergic signaling have been shown to regulate wakefulness and sleep, we examined the effects of prolonged zaleplon treatment (0.625 mg/kg for 5 days) on these systems in the hippocampus of male Wistar rats. Western blot and immunohistochemical analyses showed that the upregulated components of GABAergic signaling (glutamate decarboxylase, vesicular GABA transporter, GABA, and α1 subunit of the GABAA receptor) were accompanied by increased protein levels in the glutamatergic system (vesicular glutamate transporter 1 and NR1, NR2A, and NR2B subunits of N-methyl-d-aspartate receptor). Our results, showing that zaleplon enhances GABA neurotransmission in the hippocampus, were not surprising. However, we found that treatment also increased glutamatergic signaling. This could be the result of the downregulation of adenosine A1 receptors, important modulators of the glutamatergic system. Further studies are needed to investigate the effects of the zaleplon-induced increase in hippocampal glutamatergic neurotransmission and the possible involvement of the adenosine system in zaleplon’s mechanism of action.",
journal = "Brain Sciences",
title = "Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus",
volume = "13",
number = "12",
pages = "1707",
doi = "10.3390/brainsci13121707"
}

Martinović, J., Samardžić, J., Zarić Kontić, M., Ivković, S., Dacić, S., Major, T., Radosavljević, M.,& Svob Strac, D.. (2023). Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus. in Brain Sciences, 13(12), 1707.
https://doi.org/10.3390/brainsci13121707

Martinović J, Samardžić J, Zarić Kontić M, Ivković S, Dacić S, Major T, Radosavljević M, Svob Strac D. Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus. in Brain Sciences. 2023;13(12):1707.
doi:10.3390/brainsci13121707 .

Martinović, Jelena, Samardžić, Janko, Zarić Kontić, Marina, Ivković, Sanja, Dacić, Sanja, Major, Tamara, Radosavljević, Milica, Svob Strac, Dubravka, "Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus" in Brain Sciences, 13, no. 12 (2023):1707,
https://doi.org/10.3390/brainsci13121707 . .

TY  - CONF
AU  - Guševac Stojanović, Ivana
AU  - Dragić, Milorad
AU  - Zarić Kontić, Marina
AU  - Martinović, Jelena
AU  - Mitrović, Nataša
AU  - Stojanović, Zoran
AU  - Veljković, Filip
AU  - Martinović, D.
AU  - Grković, Ivana
AU  - Drakulić, Dunja
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11058
AB  - Cerebral hypoperfusion (CH) is recognised as a contributor to various impairments characteristic for elderly population and patients with vascular dementia and Alzheimer’s disease. CH-induced brain damage is linked with oxidative stress in the cells that can cause DNA fragmentation and cell death, reflected through a change in cells’ morphology. Our study investigated the beneficial effects of progesterone (P4), a hormone with neuroprotective properties, against CH-induced oxidative stress and neurodegenerative pathologies in rat prefrontal cortex (PFC). For the purpose of the experiment, adult male Wistar rats were dived into groups: (I) animals subjected to permanent bilateral occlusion of common carotid arteries (2VO) treated with vehicle (commercial flax oil, 1 mg/kg/day), (II) animals subjected to 2VO treated with P4 dissolved in vehicle (1.7 mg/kg/day) and (III) animals subjected to sham operation treated with vehicle. Animals were sacrificed after 7 subcutaneous treatments. Levels of pro-/antioxidant balance (PAB) and DNA fragmentation along with cell morphology were estimated by well-defined methods. The results revealed that P4 administration moderated CH-induced impairments in PFC, not only by decreasing PAB level and diminishing DNA fragmentation, but also preserving the cell morphology reflected through clearly defined cell bodies, with round nuclei, prominent nucleolus and visible Nissl bodies in layer III. Obtained results point out that P4 is able to attenuate CH-induced pro-oxidant state and subsequent changes in PFC. This hormone holds promise as an effective agent for the CH treatment, still, its specific actions remain to be discovered.
PB  - Belgrade : Serbian Neuroscience Society
C3  - 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
T1  - Progesterone treatment preserves cortical pro-/antioxidant balance, DNA integrity and cell morphology in rat cerebral hypoperfusion model
SP  - 117
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11058
ER  - 

@conference{
author = "Guševac Stojanović, Ivana and Dragić, Milorad and Zarić Kontić, Marina and Martinović, Jelena and Mitrović, Nataša and Stojanović, Zoran and Veljković, Filip and Martinović, D. and Grković, Ivana and Drakulić, Dunja",
year = "2023",
abstract = "Cerebral hypoperfusion (CH) is recognised as a contributor to various impairments characteristic for elderly population and patients with vascular dementia and Alzheimer’s disease. CH-induced brain damage is linked with oxidative stress in the cells that can cause DNA fragmentation and cell death, reflected through a change in cells’ morphology. Our study investigated the beneficial effects of progesterone (P4), a hormone with neuroprotective properties, against CH-induced oxidative stress and neurodegenerative pathologies in rat prefrontal cortex (PFC). For the purpose of the experiment, adult male Wistar rats were dived into groups: (I) animals subjected to permanent bilateral occlusion of common carotid arteries (2VO) treated with vehicle (commercial flax oil, 1 mg/kg/day), (II) animals subjected to 2VO treated with P4 dissolved in vehicle (1.7 mg/kg/day) and (III) animals subjected to sham operation treated with vehicle. Animals were sacrificed after 7 subcutaneous treatments. Levels of pro-/antioxidant balance (PAB) and DNA fragmentation along with cell morphology were estimated by well-defined methods. The results revealed that P4 administration moderated CH-induced impairments in PFC, not only by decreasing PAB level and diminishing DNA fragmentation, but also preserving the cell morphology reflected through clearly defined cell bodies, with round nuclei, prominent nucleolus and visible Nissl bodies in layer III. Obtained results point out that P4 is able to attenuate CH-induced pro-oxidant state and subsequent changes in PFC. This hormone holds promise as an effective agent for the CH treatment, still, its specific actions remain to be discovered.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade",
title = "Progesterone treatment preserves cortical pro-/antioxidant balance, DNA integrity and cell morphology in rat cerebral hypoperfusion model",
pages = "117",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11058"
}

Guševac Stojanović, I., Dragić, M., Zarić Kontić, M., Martinović, J., Mitrović, N., Stojanović, Z., Veljković, F., Martinović, D., Grković, I.,& Drakulić, D.. (2023). Progesterone treatment preserves cortical pro-/antioxidant balance, DNA integrity and cell morphology in rat cerebral hypoperfusion model. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
Belgrade : Serbian Neuroscience Society., 117.
https://hdl.handle.net/21.15107/rcub_vinar_11058

Guševac Stojanović I, Dragić M, Zarić Kontić M, Martinović J, Mitrović N, Stojanović Z, Veljković F, Martinović D, Grković I, Drakulić D. Progesterone treatment preserves cortical pro-/antioxidant balance, DNA integrity and cell morphology in rat cerebral hypoperfusion model. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade. 2023;:117.
https://hdl.handle.net/21.15107/rcub_vinar_11058 .

Guševac Stojanović, Ivana, Dragić, Milorad, Zarić Kontić, Marina, Martinović, Jelena, Mitrović, Nataša, Stojanović, Zoran, Veljković, Filip, Martinović, D., Grković, Ivana, Drakulić, Dunja, "Progesterone treatment preserves cortical pro-/antioxidant balance, DNA integrity and cell morphology in rat cerebral hypoperfusion model" in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade (2023):117,
https://hdl.handle.net/21.15107/rcub_vinar_11058 .

TY  - CONF
AU  - Grković, Ivana
AU  - Dragić, Milorad
AU  - Mitrović, Nataša
AU  - Zarić Kontić, Marina
AU  - Martinović, Jelena
AU  - Guševac Stojanović, Ivana
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11061
AB  - Adenosine 5'-triphosphate (ATP) and adenosine are versatile signaling molecules involved in many pathophysiological processes in the nervous system. They can be released from all types of brain cells in the extracellular space and activates purinergic receptors. Signaling via extracellular ATP is regulated by cell-surface located ectonucleotidases. Extracellular AMP resulting from the hydrolysis of ATP and ADP can in turn be hydrolyzed into adenosine by ecto-5'-nucleotidase (eN). We examined the involvement of purinergic signaling components in the rat model of trimethyltin (TMT)-induced hippocampal neurodegeneration (8mg/kg, single ip), which results in behavioral and neurological dysfunction similar as in Alzheimer's disease models. Enzyme histochemistry and immunohistochemistry (ir) showed that products of AMPase activity and eN-ir were accumulated in the neuronal strata, infiltrating within neuronal cell layers, depicting individual round-shaped elements that covered neuronal layers with pronounced cell death mostly at the late stage of TMT-induced neurodegeneration. Co-localization with Iba1+ specifically marked eN at amoeboid microglial cells. Neither of the tested pro-inflammatory cytokines (IL-1β, TNF-α, IL10) and C3 nor polarization marker iNOS was found in association with those Iba1/eN+ -cells. Iba1-ir cells co-localized with Arg1-ir and phagocytic marker CD68- ir. Marked induction of P2Y12R-, P2Y6R-, and P2X4-mRNA at the early stage of TMT-induced neurodegeneration might reflect the migration, and chemotaxis of microglia, while induction of P2X7R at amoeboid cells probably modulates their phagocytic role. These findings may contribute to a better understanding of the involvement of purinergic signaling components in the progression of neurodegenerative disorders that could be target molecules for development of novel therapies.
PB  - Belgrade : Serbian Neuroscience Society
C3  - 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
T1  - Ecto-5'-nucleotidase marks amoeboid microglial cells in the rat model of neurodegeneration
SP  - 120
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11061
ER  - 

@conference{
author = "Grković, Ivana and Dragić, Milorad and Mitrović, Nataša and Zarić Kontić, Marina and Martinović, Jelena and Guševac Stojanović, Ivana",
year = "2023",
abstract = "Adenosine 5'-triphosphate (ATP) and adenosine are versatile signaling molecules involved in many pathophysiological processes in the nervous system. They can be released from all types of brain cells in the extracellular space and activates purinergic receptors. Signaling via extracellular ATP is regulated by cell-surface located ectonucleotidases. Extracellular AMP resulting from the hydrolysis of ATP and ADP can in turn be hydrolyzed into adenosine by ecto-5'-nucleotidase (eN). We examined the involvement of purinergic signaling components in the rat model of trimethyltin (TMT)-induced hippocampal neurodegeneration (8mg/kg, single ip), which results in behavioral and neurological dysfunction similar as in Alzheimer's disease models. Enzyme histochemistry and immunohistochemistry (ir) showed that products of AMPase activity and eN-ir were accumulated in the neuronal strata, infiltrating within neuronal cell layers, depicting individual round-shaped elements that covered neuronal layers with pronounced cell death mostly at the late stage of TMT-induced neurodegeneration. Co-localization with Iba1+ specifically marked eN at amoeboid microglial cells. Neither of the tested pro-inflammatory cytokines (IL-1β, TNF-α, IL10) and C3 nor polarization marker iNOS was found in association with those Iba1/eN+ -cells. Iba1-ir cells co-localized with Arg1-ir and phagocytic marker CD68- ir. Marked induction of P2Y12R-, P2Y6R-, and P2X4-mRNA at the early stage of TMT-induced neurodegeneration might reflect the migration, and chemotaxis of microglia, while induction of P2X7R at amoeboid cells probably modulates their phagocytic role. These findings may contribute to a better understanding of the involvement of purinergic signaling components in the progression of neurodegenerative disorders that could be target molecules for development of novel therapies.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade",
title = "Ecto-5'-nucleotidase marks amoeboid microglial cells in the rat model of neurodegeneration",
pages = "120",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11061"
}

Grković, I., Dragić, M., Mitrović, N., Zarić Kontić, M., Martinović, J.,& Guševac Stojanović, I.. (2023). Ecto-5'-nucleotidase marks amoeboid microglial cells in the rat model of neurodegeneration. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
Belgrade : Serbian Neuroscience Society., 120.
https://hdl.handle.net/21.15107/rcub_vinar_11061

Grković I, Dragić M, Mitrović N, Zarić Kontić M, Martinović J, Guševac Stojanović I. Ecto-5'-nucleotidase marks amoeboid microglial cells in the rat model of neurodegeneration. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade. 2023;:120.
https://hdl.handle.net/21.15107/rcub_vinar_11061 .

Grković, Ivana, Dragić, Milorad, Mitrović, Nataša, Zarić Kontić, Marina, Martinović, Jelena, Guševac Stojanović, Ivana, "Ecto-5'-nucleotidase marks amoeboid microglial cells in the rat model of neurodegeneration" in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade (2023):120,
https://hdl.handle.net/21.15107/rcub_vinar_11061 .

TY  - CONF
AU  - Martinović, Jelena
AU  - Zarić Kontić, Marina
AU  - Guševac Stojanović, Ivana
AU  - Mitrović, Nataša
AU  - Grković, Ivana
AU  - Stojanović, Zoran
AU  - Drakulić, Dunja
AU  - Samardžić, Janko
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11047
AB  - Zaleplon, a member of Z-drugs, is a pyrazolopyrimidine hypnotic with sedative, anxiolytic, anticonvulsant and muscle relaxant properties. Zaleplon is approved for the short-term management of insomnia since acting as positive γ-aminobutyric acid (GABA) receptor allosteric modulator increases efficacy of inhibition on brain excitability. Importantly, for the proper functioning of the brain a balance between inhibitory (i.e., GABAergic) and excitatory (i.e., glutamatergic) system must be accomplished. This may be fulfilled by control of presynaptic elements (synthesis or degradation of glutamate and GABA neurotransmitters, their compartmentation, releasing and recycling) and regulation of expression and function of glutamate and GABA receptors. Hence, we aimed to investigate effects of prolonged zaleplon treatment on the expression of proteins involved in the gabaergic and glutamatergic signalization in the hippocampus of adult male Wistar rats. Five-day intraperitoneal administration increased level of components of GABAergic signalization (glutamate decarboxylase 67-GAD67, vesicular GABA transporter-VGAT and α1 subunit of GABA receptor-GABAAα1). This was accompanied by increased level of glutamatergic components (vesicular glutamate transporter 1-vGlut1 and subunits of glutamate N-Methyl-d-aspartate receptor-NMDAR, namely NR1, NR2A, NR2B), which clearly indicate maintenance of balance between main inhibitory and excitatory neurotransmitters. Given the importance of equilibrium of these systems for neuronal excitability, synaptic plasticity and cognitive functions, as well as its involvement in the mood, feeding behavior, reproductive functions, pain sensitivity, aging, etc., the current and prospective pharmaceuticals increasingly rely on GABA/glutamate balance
PB  - Belgrade : Serbian Neuroscience Society
C3  - 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
T1  - Prolonged zaleplon treatment enhance GABAergic and glutamatergic signaling in the hippocampus of male Wistar rats
SP  - 59
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11047
ER  - 

@conference{
author = "Martinović, Jelena and Zarić Kontić, Marina and Guševac Stojanović, Ivana and Mitrović, Nataša and Grković, Ivana and Stojanović, Zoran and Drakulić, Dunja and Samardžić, Janko",
year = "2023",
abstract = "Zaleplon, a member of Z-drugs, is a pyrazolopyrimidine hypnotic with sedative, anxiolytic, anticonvulsant and muscle relaxant properties. Zaleplon is approved for the short-term management of insomnia since acting as positive γ-aminobutyric acid (GABA) receptor allosteric modulator increases efficacy of inhibition on brain excitability. Importantly, for the proper functioning of the brain a balance between inhibitory (i.e., GABAergic) and excitatory (i.e., glutamatergic) system must be accomplished. This may be fulfilled by control of presynaptic elements (synthesis or degradation of glutamate and GABA neurotransmitters, their compartmentation, releasing and recycling) and regulation of expression and function of glutamate and GABA receptors. Hence, we aimed to investigate effects of prolonged zaleplon treatment on the expression of proteins involved in the gabaergic and glutamatergic signalization in the hippocampus of adult male Wistar rats. Five-day intraperitoneal administration increased level of components of GABAergic signalization (glutamate decarboxylase 67-GAD67, vesicular GABA transporter-VGAT and α1 subunit of GABA receptor-GABAAα1). This was accompanied by increased level of glutamatergic components (vesicular glutamate transporter 1-vGlut1 and subunits of glutamate N-Methyl-d-aspartate receptor-NMDAR, namely NR1, NR2A, NR2B), which clearly indicate maintenance of balance between main inhibitory and excitatory neurotransmitters. Given the importance of equilibrium of these systems for neuronal excitability, synaptic plasticity and cognitive functions, as well as its involvement in the mood, feeding behavior, reproductive functions, pain sensitivity, aging, etc., the current and prospective pharmaceuticals increasingly rely on GABA/glutamate balance",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade",
title = "Prolonged zaleplon treatment enhance GABAergic and glutamatergic signaling in the hippocampus of male Wistar rats",
pages = "59",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11047"
}

Martinović, J., Zarić Kontić, M., Guševac Stojanović, I., Mitrović, N., Grković, I., Stojanović, Z., Drakulić, D.,& Samardžić, J.. (2023). Prolonged zaleplon treatment enhance GABAergic and glutamatergic signaling in the hippocampus of male Wistar rats. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
Belgrade : Serbian Neuroscience Society., 59.
https://hdl.handle.net/21.15107/rcub_vinar_11047

Martinović J, Zarić Kontić M, Guševac Stojanović I, Mitrović N, Grković I, Stojanović Z, Drakulić D, Samardžić J. Prolonged zaleplon treatment enhance GABAergic and glutamatergic signaling in the hippocampus of male Wistar rats. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade. 2023;:59.
https://hdl.handle.net/21.15107/rcub_vinar_11047 .

Martinović, Jelena, Zarić Kontić, Marina, Guševac Stojanović, Ivana, Mitrović, Nataša, Grković, Ivana, Stojanović, Zoran, Drakulić, Dunja, Samardžić, Janko, "Prolonged zaleplon treatment enhance GABAergic and glutamatergic signaling in the hippocampus of male Wistar rats" in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade (2023):59,
https://hdl.handle.net/21.15107/rcub_vinar_11047 .

TY  - CONF
AU  - Adžić Bukvić, Marija
AU  - Dragić, Milorad
AU  - Zarić Kontić, Marina
AU  - Nedeljković, Nadežda
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11055
AB  - The antibiotic streptozotocin (STZ) is an FDA approved for pancreatic neuroendocrine tumors. It has also been used for rat model of diabetes induction, where it causes a progressive increase in BBB permeability, and activates glial cells. In intracerebroventricular injected STZ-induced AD model, the abnormal mitochondrial morphology, decrease ATP biosynthesis, accumulation of reactive oxygen species (ROS), disrupted homeostasis of brain insulin signaling and defect in cerebral glucose metabolism were observed. Streptozotocin has been used to induce mitochondrial, endoplasmic and in general oxidative stress in neuronal cells and in astrocytoma C6 cell line in vitro. Our study aimed to analyze the STZ effects on primary rat astrocyte cultures. The testing of STZ concentration range (1, 5, 10 and 20 mM) in MTT assay, excluded the 20 mM STZ which evoked a significant decrease in mitochondrial activity in astrocytes. As ROS are the most pronounced parameters elevated in STZ disease modeling, we analyzed GSH, SH groups and MDA 24 h after the STZ application. The 10 mM STZ lowered GSH levels, while SH groups showed a STZ dose dependent decrease. On the other hand, MDA showed a slight, but not significant increase following STZ concentration increase. Moreover, we investigated changes in the purinergic signaling system. Our results show the drop of CD73 activity 24 h after the 10 mM STZ treatment, accompanied by CD73 immunofluorescence decrease on the astrocyte membranes. Similarly, nucleoside triphosphate diphosphohydrolase 2 (NT2) was downregulated on astrocyte membranes. These results encourage further analysis of the P1 and P2 purinergic receptors
PB  - Belgrade : Serbian Neuroscience Society
C3  - 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
T1  - Streptozotocin, an FDA approved drug, affects the oxidative stress parameters and purinergic signaling components in primary rat astrocyte cultures
SP  - 102
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11055
ER  - 

@conference{
author = "Adžić Bukvić, Marija and Dragić, Milorad and Zarić Kontić, Marina and Nedeljković, Nadežda",
year = "2023",
abstract = "The antibiotic streptozotocin (STZ) is an FDA approved for pancreatic neuroendocrine tumors. It has also been used for rat model of diabetes induction, where it causes a progressive increase in BBB permeability, and activates glial cells. In intracerebroventricular injected STZ-induced AD model, the abnormal mitochondrial morphology, decrease ATP biosynthesis, accumulation of reactive oxygen species (ROS), disrupted homeostasis of brain insulin signaling and defect in cerebral glucose metabolism were observed. Streptozotocin has been used to induce mitochondrial, endoplasmic and in general oxidative stress in neuronal cells and in astrocytoma C6 cell line in vitro. Our study aimed to analyze the STZ effects on primary rat astrocyte cultures. The testing of STZ concentration range (1, 5, 10 and 20 mM) in MTT assay, excluded the 20 mM STZ which evoked a significant decrease in mitochondrial activity in astrocytes. As ROS are the most pronounced parameters elevated in STZ disease modeling, we analyzed GSH, SH groups and MDA 24 h after the STZ application. The 10 mM STZ lowered GSH levels, while SH groups showed a STZ dose dependent decrease. On the other hand, MDA showed a slight, but not significant increase following STZ concentration increase. Moreover, we investigated changes in the purinergic signaling system. Our results show the drop of CD73 activity 24 h after the 10 mM STZ treatment, accompanied by CD73 immunofluorescence decrease on the astrocyte membranes. Similarly, nucleoside triphosphate diphosphohydrolase 2 (NT2) was downregulated on astrocyte membranes. These results encourage further analysis of the P1 and P2 purinergic receptors",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade",
title = "Streptozotocin, an FDA approved drug, affects the oxidative stress parameters and purinergic signaling components in primary rat astrocyte cultures",
pages = "102",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11055"
}

Adžić Bukvić, M., Dragić, M., Zarić Kontić, M.,& Nedeljković, N.. (2023). Streptozotocin, an FDA approved drug, affects the oxidative stress parameters and purinergic signaling components in primary rat astrocyte cultures. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
Belgrade : Serbian Neuroscience Society., 102.
https://hdl.handle.net/21.15107/rcub_vinar_11055

Adžić Bukvić M, Dragić M, Zarić Kontić M, Nedeljković N. Streptozotocin, an FDA approved drug, affects the oxidative stress parameters and purinergic signaling components in primary rat astrocyte cultures. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade. 2023;:102.
https://hdl.handle.net/21.15107/rcub_vinar_11055 .

Adžić Bukvić, Marija, Dragić, Milorad, Zarić Kontić, Marina, Nedeljković, Nadežda, "Streptozotocin, an FDA approved drug, affects the oxidative stress parameters and purinergic signaling components in primary rat astrocyte cultures" in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade (2023):102,
https://hdl.handle.net/21.15107/rcub_vinar_11055 .

TY  - CONF
AU  - Zarić Kontić, Marina
AU  - Dragić, Milorad
AU  - Martinović, Jelena
AU  - Mihajlović, Katarina
AU  - Brkić, Željka
AU  - Mitrović, Nataša
AU  - Guševac Stojanović, Ivana
AU  - Grković, Ivana
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11048
AB  - The benzodiazepine alprazolam (ALP) is commonly prescribed to treat anxiety, panic, and sleep disorders. However, ALP is often abused for prolonged periods of time, leading to severe side effects such as tolerance, dependence, and withdrawal syndrome. Previous literature data suggest that neuroadaptive changes at synaptic receptors, such as gammaaminobutyric acid receptor type A (GABAAR) and glutamatergic receptors, may be responsible for the occurrence and development of the aforementioned side effects. Therefore, the present study investigated the potential effects of prolonged ALP treatment (2 mg/kg, ip.) on the α1-subunit containing GABAAR and components of glutamatergic neurotransmission in the hippocampus of adult male Wistar rats. The study revealed behavioral changes consistent with a possible onset of tolerance and associated changes in the GABAergic and glutamatergic systems. The primary target of ALP, the α1-subunit containing GABAAR, was decreased indicating its potential downregulation by prolonged agonist (ALP) action. Considering studied glutamatergic components, an increase in NMDAR subunits, a decrease in vGlut1, and differential modulation of excitatory amino acid transporters 1 and 2 (EAAT1/2, in vivo and in vitro) were observed. These changes may all together indicate a compensatory mechanism due to the sustained suppression of glutamatergic neurons by enhanced inhibitory impulses from GABAergic neurons. The data presented provide valuable and, to our knowledge, the first information on components of glutamatergic neurotransmission after prolonged ALP treatment and their potential impact on the development of side effects. However, further research is needed to examine the observed changes in detail.
PB  - Belgrade : Serbian Neurocardiological Society
C3  - 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
T1  - Long-term alprazolam treatment may cause tolerance development by modulating components of glutamatergic neurotransmission in the hippocampus of male Wistar rats
SP  - 60
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11048
ER  - 

@conference{
author = "Zarić Kontić, Marina and Dragić, Milorad and Martinović, Jelena and Mihajlović, Katarina and Brkić, Željka and Mitrović, Nataša and Guševac Stojanović, Ivana and Grković, Ivana",
year = "2023",
abstract = "The benzodiazepine alprazolam (ALP) is commonly prescribed to treat anxiety, panic, and sleep disorders. However, ALP is often abused for prolonged periods of time, leading to severe side effects such as tolerance, dependence, and withdrawal syndrome. Previous literature data suggest that neuroadaptive changes at synaptic receptors, such as gammaaminobutyric acid receptor type A (GABAAR) and glutamatergic receptors, may be responsible for the occurrence and development of the aforementioned side effects. Therefore, the present study investigated the potential effects of prolonged ALP treatment (2 mg/kg, ip.) on the α1-subunit containing GABAAR and components of glutamatergic neurotransmission in the hippocampus of adult male Wistar rats. The study revealed behavioral changes consistent with a possible onset of tolerance and associated changes in the GABAergic and glutamatergic systems. The primary target of ALP, the α1-subunit containing GABAAR, was decreased indicating its potential downregulation by prolonged agonist (ALP) action. Considering studied glutamatergic components, an increase in NMDAR subunits, a decrease in vGlut1, and differential modulation of excitatory amino acid transporters 1 and 2 (EAAT1/2, in vivo and in vitro) were observed. These changes may all together indicate a compensatory mechanism due to the sustained suppression of glutamatergic neurons by enhanced inhibitory impulses from GABAergic neurons. The data presented provide valuable and, to our knowledge, the first information on components of glutamatergic neurotransmission after prolonged ALP treatment and their potential impact on the development of side effects. However, further research is needed to examine the observed changes in detail.",
publisher = "Belgrade : Serbian Neurocardiological Society",
journal = "8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade",
title = "Long-term alprazolam treatment may cause tolerance development by modulating components of glutamatergic neurotransmission in the hippocampus of male Wistar rats",
pages = "60",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11048"
}

Zarić Kontić, M., Dragić, M., Martinović, J., Mihajlović, K., Brkić, Ž., Mitrović, N., Guševac Stojanović, I.,& Grković, I.. (2023). Long-term alprazolam treatment may cause tolerance development by modulating components of glutamatergic neurotransmission in the hippocampus of male Wistar rats. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
Belgrade : Serbian Neurocardiological Society., 60.
https://hdl.handle.net/21.15107/rcub_vinar_11048

Zarić Kontić M, Dragić M, Martinović J, Mihajlović K, Brkić Ž, Mitrović N, Guševac Stojanović I, Grković I. Long-term alprazolam treatment may cause tolerance development by modulating components of glutamatergic neurotransmission in the hippocampus of male Wistar rats. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade. 2023;:60.
https://hdl.handle.net/21.15107/rcub_vinar_11048 .

Zarić Kontić, Marina, Dragić, Milorad, Martinović, Jelena, Mihajlović, Katarina, Brkić, Željka, Mitrović, Nataša, Guševac Stojanović, Ivana, Grković, Ivana, "Long-term alprazolam treatment may cause tolerance development by modulating components of glutamatergic neurotransmission in the hippocampus of male Wistar rats" in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade (2023):60,
https://hdl.handle.net/21.15107/rcub_vinar_11048 .

TY  - JOUR
AU  - Martinović, Jelena
AU  - Zarić Kontić, Marina
AU  - Dragić, Milorad
AU  - Todorović, Ana
AU  - Guševac Stojanović, Ivana
AU  - Mitrović, Nataša
AU  - Grković, Ivana
AU  - Drakulić, Dunja R.
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10461
AB  - D-galactose (d-gal) is broadly used in animal aging studies as its chronic administration mimics learning and memory impairments related to aging in humans. However, within the few studies that utilize chronic oral d-gal intake, none of them is focused on alteration in synaptic structure and function. We examined the effects of 6-weeks oral d-gal intake (200 mg/kg and 500 mg/kg, dissolved in tap water) on age-related changes, with emphasis on the prefrontal cortex (PFC) and hippocampus (HIP) of adult male Wistar rats. Memory assessment was followed by histological examination of the PFC and HIP (Nissl staining and Iba-1 immunostaining), while in crude synaptosomal fractions the state of oxidative stress and the expression of proteins involved in glutamatergic signaling was determined. Although applied dosages compromised memory, alterations such as impaired sensory-motor function and aberrant morphology were not detected. In the PFC, analysis of microglia revealed reduction of branching pattern following d-gal intake, in parallel with increased oxidative damage of proteins, lipids and disturbed pro-oxidant antioxidant balance. These changes in the PFC were further accompanied with decreased levels of vesicular glutamate transporter 1, syntaxin-1 and NMDA receptor 2B subunit in both treated groups. Simultaneously, the increased hippocampal oxidative damage of lipids was detected. Results indicate successful provocation of age-related changes following oral d-gal intake, and suggest greater sensitivity of the PFC to d-gal treatment than HIP.
T2  - Behavioural Brain Research
T1  - Chronic oral d-galactose intake provokes age-related changes in the rat prefrontal cortex
VL  - 436
SP  - 114072
DO  - 10.1016/j.bbr.2022.114072
ER  - 

@article{
author = "Martinović, Jelena and Zarić Kontić, Marina and Dragić, Milorad and Todorović, Ana and Guševac Stojanović, Ivana and Mitrović, Nataša and Grković, Ivana and Drakulić, Dunja R.",
year = "2023",
abstract = "D-galactose (d-gal) is broadly used in animal aging studies as its chronic administration mimics learning and memory impairments related to aging in humans. However, within the few studies that utilize chronic oral d-gal intake, none of them is focused on alteration in synaptic structure and function. We examined the effects of 6-weeks oral d-gal intake (200 mg/kg and 500 mg/kg, dissolved in tap water) on age-related changes, with emphasis on the prefrontal cortex (PFC) and hippocampus (HIP) of adult male Wistar rats. Memory assessment was followed by histological examination of the PFC and HIP (Nissl staining and Iba-1 immunostaining), while in crude synaptosomal fractions the state of oxidative stress and the expression of proteins involved in glutamatergic signaling was determined. Although applied dosages compromised memory, alterations such as impaired sensory-motor function and aberrant morphology were not detected. In the PFC, analysis of microglia revealed reduction of branching pattern following d-gal intake, in parallel with increased oxidative damage of proteins, lipids and disturbed pro-oxidant antioxidant balance. These changes in the PFC were further accompanied with decreased levels of vesicular glutamate transporter 1, syntaxin-1 and NMDA receptor 2B subunit in both treated groups. Simultaneously, the increased hippocampal oxidative damage of lipids was detected. Results indicate successful provocation of age-related changes following oral d-gal intake, and suggest greater sensitivity of the PFC to d-gal treatment than HIP.",
journal = "Behavioural Brain Research",
title = "Chronic oral d-galactose intake provokes age-related changes in the rat prefrontal cortex",
volume = "436",
pages = "114072",
doi = "10.1016/j.bbr.2022.114072"
}

Martinović, J., Zarić Kontić, M., Dragić, M., Todorović, A., Guševac Stojanović, I., Mitrović, N., Grković, I.,& Drakulić, D. R.. (2023). Chronic oral d-galactose intake provokes age-related changes in the rat prefrontal cortex. in Behavioural Brain Research, 436, 114072.
https://doi.org/10.1016/j.bbr.2022.114072

Martinović J, Zarić Kontić M, Dragić M, Todorović A, Guševac Stojanović I, Mitrović N, Grković I, Drakulić DR. Chronic oral d-galactose intake provokes age-related changes in the rat prefrontal cortex. in Behavioural Brain Research. 2023;436:114072.
doi:10.1016/j.bbr.2022.114072 .

Martinović, Jelena, Zarić Kontić, Marina, Dragić, Milorad, Todorović, Ana, Guševac Stojanović, Ivana, Mitrović, Nataša, Grković, Ivana, Drakulić, Dunja R., "Chronic oral d-galactose intake provokes age-related changes in the rat prefrontal cortex" in Behavioural Brain Research, 436 (2023):114072,
https://doi.org/10.1016/j.bbr.2022.114072 . .

TY  - JOUR
AU  - Zarić Kontić, Marina
AU  - Dragić, Milorad
AU  - Martinović, Jelena
AU  - Mihajlović, Katarina
AU  - Brkić, Željka
AU  - Mitrović, Nataša
AU  - Grković, Ivana
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11160
AB  - Alprazolam (ALP), a benzodiazepine (BDZ) used to treat anxiety, panic, and sleep disorders, is one of the most prescribed psychotropic drugs worldwide. The side effects associated with long-term (mis)use of ALP have become a major challenge in pharmacotherapy, emphasizing the unmet need to further investigate their underlying molecular mechanisms. Prolonged BDZ exposure may induce adaptive changes in the function of several receptors, including the primary target, gammaaminobutyric acid receptor type A (GABAAR), but also other neurotransmitter receptors such as glutamatergic. The present study investigated the potential effects of prolonged ALP treatment on components of glutamatergic neurotransmission, with special emphasis on N-Methyl-D-aspartate receptor (NMDAR) in the hippocampus of adult male Wistar rats. The study revealed behavioral changes consistent with potential onset of tolerance and involvement of the glutamatergic system in its development. Specifically, an increase in NMDAR subunits (NR1, NR2A, NR2B), a decrease in vesicular glutamate transporter 1 (vGlut1), and differential modulation of excitatory amino acid transporters 1 and 2 (EAAT1/2, in vivo and in vitro) were observed, alongside a decrease in α1-containing GABAAR following the treatment. By describing the development of compensatory actions in the glutamatergic system, the present study provides valuable information on neuroadaptive mechanisms following prolonged ALP intake.
T2  - Pharmaceuticals
T1  - Prolonged Alprazolam Treatment Alters Components of Glutamatergic Neurotransmission in the Hippocampus of Male Wistar Rats—The Neuroadaptive Changes following Long-Term Benzodiazepine (Mis)Use
VL  - 16
IS  - 3
SP  - 331
DO  - 10.3390/ph16030331
ER  - 

@article{
author = "Zarić Kontić, Marina and Dragić, Milorad and Martinović, Jelena and Mihajlović, Katarina and Brkić, Željka and Mitrović, Nataša and Grković, Ivana",
year = "2023",
abstract = "Alprazolam (ALP), a benzodiazepine (BDZ) used to treat anxiety, panic, and sleep disorders, is one of the most prescribed psychotropic drugs worldwide. The side effects associated with long-term (mis)use of ALP have become a major challenge in pharmacotherapy, emphasizing the unmet need to further investigate their underlying molecular mechanisms. Prolonged BDZ exposure may induce adaptive changes in the function of several receptors, including the primary target, gammaaminobutyric acid receptor type A (GABAAR), but also other neurotransmitter receptors such as glutamatergic. The present study investigated the potential effects of prolonged ALP treatment on components of glutamatergic neurotransmission, with special emphasis on N-Methyl-D-aspartate receptor (NMDAR) in the hippocampus of adult male Wistar rats. The study revealed behavioral changes consistent with potential onset of tolerance and involvement of the glutamatergic system in its development. Specifically, an increase in NMDAR subunits (NR1, NR2A, NR2B), a decrease in vesicular glutamate transporter 1 (vGlut1), and differential modulation of excitatory amino acid transporters 1 and 2 (EAAT1/2, in vivo and in vitro) were observed, alongside a decrease in α1-containing GABAAR following the treatment. By describing the development of compensatory actions in the glutamatergic system, the present study provides valuable information on neuroadaptive mechanisms following prolonged ALP intake.",
journal = "Pharmaceuticals",
title = "Prolonged Alprazolam Treatment Alters Components of Glutamatergic Neurotransmission in the Hippocampus of Male Wistar Rats—The Neuroadaptive Changes following Long-Term Benzodiazepine (Mis)Use",
volume = "16",
number = "3",
pages = "331",
doi = "10.3390/ph16030331"
}

Zarić Kontić, M., Dragić, M., Martinović, J., Mihajlović, K., Brkić, Ž., Mitrović, N.,& Grković, I.. (2023). Prolonged Alprazolam Treatment Alters Components of Glutamatergic Neurotransmission in the Hippocampus of Male Wistar Rats—The Neuroadaptive Changes following Long-Term Benzodiazepine (Mis)Use. in Pharmaceuticals, 16(3), 331.
https://doi.org/10.3390/ph16030331

Zarić Kontić M, Dragić M, Martinović J, Mihajlović K, Brkić Ž, Mitrović N, Grković I. Prolonged Alprazolam Treatment Alters Components of Glutamatergic Neurotransmission in the Hippocampus of Male Wistar Rats—The Neuroadaptive Changes following Long-Term Benzodiazepine (Mis)Use. in Pharmaceuticals. 2023;16(3):331.
doi:10.3390/ph16030331 .

Zarić Kontić, Marina, Dragić, Milorad, Martinović, Jelena, Mihajlović, Katarina, Brkić, Željka, Mitrović, Nataša, Grković, Ivana, "Prolonged Alprazolam Treatment Alters Components of Glutamatergic Neurotransmission in the Hippocampus of Male Wistar Rats—The Neuroadaptive Changes following Long-Term Benzodiazepine (Mis)Use" in Pharmaceuticals, 16, no. 3 (2023):331,
https://doi.org/10.3390/ph16030331 . .

TY  - JOUR
AU  - Zeljković Jovanović, Milica
AU  - Stanojević, Jelena
AU  - Stevanović, Ivana
AU  - Stekić, Anđela
AU  - Bolland, Samuel J.
AU  - Jasnić, Nebojša
AU  - Ninković, Milica
AU  - Zarić Kontić, Marina
AU  - Ilić, Tihomir V.
AU  - Rodger, Jennifer
AU  - Nedeljković, Nadežda
AU  - Dragić, Milorad
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11099
AB  - Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by the progressive degeneration of the dopaminergic system, leading to a variety of motor and nonmotor symptoms. The currently available symptomatic therapy loses efficacy over time, indicating the need for new therapeutic approaches. Repetitive transcranial magnetic stimulation (rTMS) has emerged as one of the potential candidates for PD therapy. Intermittent theta burst stimulation (iTBS), an excitatory protocol of rTMS, has been shown to be beneficial in several animal models of neurodegeneration, including PD. The aim of this study was to investigate the effects of prolonged iTBS on motor performance and behavior and the possible association with changes in the NMDAR subunit composition in the 6-hydroxydopamine (6-OHDA)-induced experimental model of PD. Two-month-old male Wistar rats were divided into four groups: controls, 6-OHDA rats, 6-OHDA + iTBS protocol (two times/day/three weeks) and the sham group. The therapeutic effect of iTBS was evaluated by examining motor coordination, balance, spontaneous forelimb use, exploratory behavior, anxiety-like, depressive/anhedonic-like behavior and short-term memory, histopathological changes and changes at the molecular level. We demonstrated the positive effects of iTBS at both motor and behavioral levels. In addition, the beneficial effects were reflected in reduced degeneration of dopaminergic neurons and a subsequent increase in the level of DA in the caudoputamen. Finally, iTBS altered protein expression and NMDAR subunit composition, suggesting a sustained effect. Applied early in the disease course, the iTBS protocol may be a promising candidate for early-stage PD therapy, affecting motor and nonmotor deficits. © 2023 by the authors.
T2  - Cells
T1  - Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease
VL  - 12
IS  - 11
DO  - 10.3390/cells12111525
ER  - 

@article{
author = "Zeljković Jovanović, Milica and Stanojević, Jelena and Stevanović, Ivana and Stekić, Anđela and Bolland, Samuel J. and Jasnić, Nebojša and Ninković, Milica and Zarić Kontić, Marina and Ilić, Tihomir V. and Rodger, Jennifer and Nedeljković, Nadežda and Dragić, Milorad",
year = "2023",
abstract = "Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by the progressive degeneration of the dopaminergic system, leading to a variety of motor and nonmotor symptoms. The currently available symptomatic therapy loses efficacy over time, indicating the need for new therapeutic approaches. Repetitive transcranial magnetic stimulation (rTMS) has emerged as one of the potential candidates for PD therapy. Intermittent theta burst stimulation (iTBS), an excitatory protocol of rTMS, has been shown to be beneficial in several animal models of neurodegeneration, including PD. The aim of this study was to investigate the effects of prolonged iTBS on motor performance and behavior and the possible association with changes in the NMDAR subunit composition in the 6-hydroxydopamine (6-OHDA)-induced experimental model of PD. Two-month-old male Wistar rats were divided into four groups: controls, 6-OHDA rats, 6-OHDA + iTBS protocol (two times/day/three weeks) and the sham group. The therapeutic effect of iTBS was evaluated by examining motor coordination, balance, spontaneous forelimb use, exploratory behavior, anxiety-like, depressive/anhedonic-like behavior and short-term memory, histopathological changes and changes at the molecular level. We demonstrated the positive effects of iTBS at both motor and behavioral levels. In addition, the beneficial effects were reflected in reduced degeneration of dopaminergic neurons and a subsequent increase in the level of DA in the caudoputamen. Finally, iTBS altered protein expression and NMDAR subunit composition, suggesting a sustained effect. Applied early in the disease course, the iTBS protocol may be a promising candidate for early-stage PD therapy, affecting motor and nonmotor deficits. © 2023 by the authors.",
journal = "Cells",
title = "Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease",
volume = "12",
number = "11",
doi = "10.3390/cells12111525"
}

Zeljković Jovanović, M., Stanojević, J., Stevanović, I., Stekić, A., Bolland, S. J., Jasnić, N., Ninković, M., Zarić Kontić, M., Ilić, T. V., Rodger, J., Nedeljković, N.,& Dragić, M.. (2023). Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease. in Cells, 12(11).
https://doi.org/10.3390/cells12111525

Zeljković Jovanović M, Stanojević J, Stevanović I, Stekić A, Bolland SJ, Jasnić N, Ninković M, Zarić Kontić M, Ilić TV, Rodger J, Nedeljković N, Dragić M. Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease. in Cells. 2023;12(11).
doi:10.3390/cells12111525 .

Zeljković Jovanović, Milica, Stanojević, Jelena, Stevanović, Ivana, Stekić, Anđela, Bolland, Samuel J., Jasnić, Nebojša, Ninković, Milica, Zarić Kontić, Marina, Ilić, Tihomir V., Rodger, Jennifer, Nedeljković, Nadežda, Dragić, Milorad, "Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease" in Cells, 12, no. 11 (2023),
https://doi.org/10.3390/cells12111525 . .

TY  - JOUR
AU  - Stekić, Anđela
AU  - Zeljković, Milica
AU  - Zarić Kontić, Marina
AU  - Mihajlović, Katarina
AU  - Adžić, Marija
AU  - Stevanović, Ivana
AU  - Ninković, Milica
AU  - Grković, Ivana
AU  - Ilić, Tihomir V.
AU  - Nedeljković, Nadežda
AU  - Dragić, Milorad
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11159
AB  - Neurodegeneration implies progressive neuronal loss and neuroinflammation further contributing to pathology progression. It is a feature of many neurological disorders, most common being Alzheimer’s disease (AD). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive stimulation which modulates excitability of stimulated brain areas through magnetic pulses. Numerous studies indicated beneficial effect of rTMS in several neurological diseases, including AD, however, exact mechanism are yet to be elucidated. We aimed to evaluate the effect of intermittent theta burst stimulation (iTBS), an rTMS paradigm, on behavioral, neurochemical and molecular level in trimethyltin (TMT)-induced Alzheimer’s-like disease model. TMT acts as a neurotoxic agent targeting hippocampus causing cognitive impairment and neuroinflammation, replicating behavioral and molecular aspects of AD. Male Wistar rats were divided into four experimental groups–controls, rats subjected to a single dose of TMT (8 mg/kg), TMT rats subjected to iTBS two times per day for 15 days and TMT sham group. After 3 weeks, we examined exploratory behavior and memory, histopathological and changes on molecular level. TMT-treated rats exhibited severe and cognitive deficit. iTBS-treated animals showed improved cognition. iTBS reduced TMT-induced inflammation and increased anti-inflammatory molecules. We examined PI3K/Akt/mTOR signaling pathway which is involved in regulation of apoptosis, cell growth and learning and memory. We found significant downregulation of phosphorylated forms of Akt and mTOR in TMT-intoxicated animals, which were reverted following iTBS stimulation. Application of iTBS produces beneficial effects on cognition in of rats with TMT-induced hippocampal neurodegeneration and that effect could be mediated via PI3K/Akt/mTOR signaling pathway, which could candidate this protocol as a potential therapeutic approach in neurodegenerative diseases such as AD.
T2  - Frontiers in Aging Neuroscience
T1  - Intermittent Theta Burst Stimulation Ameliorates Cognitive Deficit and Attenuates Neuroinflammation via PI3K/Akt/mTOR Signaling Pathway in Alzheimer’s-Like Disease Model
VL  - 14
DO  - 10.3389/fnagi.2022.889983
ER  - 

@article{
author = "Stekić, Anđela and Zeljković, Milica and Zarić Kontić, Marina and Mihajlović, Katarina and Adžić, Marija and Stevanović, Ivana and Ninković, Milica and Grković, Ivana and Ilić, Tihomir V. and Nedeljković, Nadežda and Dragić, Milorad",
year = "2022",
abstract = "Neurodegeneration implies progressive neuronal loss and neuroinflammation further contributing to pathology progression. It is a feature of many neurological disorders, most common being Alzheimer’s disease (AD). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive stimulation which modulates excitability of stimulated brain areas through magnetic pulses. Numerous studies indicated beneficial effect of rTMS in several neurological diseases, including AD, however, exact mechanism are yet to be elucidated. We aimed to evaluate the effect of intermittent theta burst stimulation (iTBS), an rTMS paradigm, on behavioral, neurochemical and molecular level in trimethyltin (TMT)-induced Alzheimer’s-like disease model. TMT acts as a neurotoxic agent targeting hippocampus causing cognitive impairment and neuroinflammation, replicating behavioral and molecular aspects of AD. Male Wistar rats were divided into four experimental groups–controls, rats subjected to a single dose of TMT (8 mg/kg), TMT rats subjected to iTBS two times per day for 15 days and TMT sham group. After 3 weeks, we examined exploratory behavior and memory, histopathological and changes on molecular level. TMT-treated rats exhibited severe and cognitive deficit. iTBS-treated animals showed improved cognition. iTBS reduced TMT-induced inflammation and increased anti-inflammatory molecules. We examined PI3K/Akt/mTOR signaling pathway which is involved in regulation of apoptosis, cell growth and learning and memory. We found significant downregulation of phosphorylated forms of Akt and mTOR in TMT-intoxicated animals, which were reverted following iTBS stimulation. Application of iTBS produces beneficial effects on cognition in of rats with TMT-induced hippocampal neurodegeneration and that effect could be mediated via PI3K/Akt/mTOR signaling pathway, which could candidate this protocol as a potential therapeutic approach in neurodegenerative diseases such as AD.",
journal = "Frontiers in Aging Neuroscience",
title = "Intermittent Theta Burst Stimulation Ameliorates Cognitive Deficit and Attenuates Neuroinflammation via PI3K/Akt/mTOR Signaling Pathway in Alzheimer’s-Like Disease Model",
volume = "14",
doi = "10.3389/fnagi.2022.889983"
}

Stekić, A., Zeljković, M., Zarić Kontić, M., Mihajlović, K., Adžić, M., Stevanović, I., Ninković, M., Grković, I., Ilić, T. V., Nedeljković, N.,& Dragić, M.. (2022). Intermittent Theta Burst Stimulation Ameliorates Cognitive Deficit and Attenuates Neuroinflammation via PI3K/Akt/mTOR Signaling Pathway in Alzheimer’s-Like Disease Model. in Frontiers in Aging Neuroscience, 14.
https://doi.org/10.3389/fnagi.2022.889983

Stekić A, Zeljković M, Zarić Kontić M, Mihajlović K, Adžić M, Stevanović I, Ninković M, Grković I, Ilić TV, Nedeljković N, Dragić M. Intermittent Theta Burst Stimulation Ameliorates Cognitive Deficit and Attenuates Neuroinflammation via PI3K/Akt/mTOR Signaling Pathway in Alzheimer’s-Like Disease Model. in Frontiers in Aging Neuroscience. 2022;14.
doi:10.3389/fnagi.2022.889983 .

Stekić, Anđela, Zeljković, Milica, Zarić Kontić, Marina, Mihajlović, Katarina, Adžić, Marija, Stevanović, Ivana, Ninković, Milica, Grković, Ivana, Ilić, Tihomir V., Nedeljković, Nadežda, Dragić, Milorad, "Intermittent Theta Burst Stimulation Ameliorates Cognitive Deficit and Attenuates Neuroinflammation via PI3K/Akt/mTOR Signaling Pathway in Alzheimer’s-Like Disease Model" in Frontiers in Aging Neuroscience, 14 (2022),
https://doi.org/10.3389/fnagi.2022.889983 . .

TY  - JOUR
AU  - Dragić, Milorad
AU  - Stekić, Anđela
AU  - Zeljković, Milica
AU  - Zarić Kontić, Marina
AU  - Mihajlović, Katarina
AU  - Adžić, Marija
AU  - Grković, Ivana
AU  - Nedeljković, Nadežda
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10222
AB  - The present study demonstrates altered topographic distribution and enhanced neuronal expression of major adenosine-metabolizing enzymes, i.e. ecto-5ʹ-nucleotidase (eN) and tissue non-specific alkaline phosphatase (TNAP), as well as adenosine receptor subtype A2A in the hippocampus and cortex of male rats from early to late adulthood (3, 6, 12 and 15 months old males). The significant effect of age was demonstrated for the increase in the activity and the protein expression of eN and TNAP. At 15-m, enzyme histochemistry demonstrated enhanced expression of eN in synapse-rich hippocampal and cortical layers, whereas the upsurge of TNAP was observed in the hippocampal and cortical neuropil, rather than in cells and layers where two enzymes mostly reside in 3-m old brain. Furthermore, a dichotomy in A1R and A2AR expression was demonstrated in the cortex and hippocampus from early to late adulthood. Specifically, a decrease in A1R and enhancement of A2AR expression were demonstrated by immunohistochemistry, the latter being almost exclusively localized in hippocampal pyramidal and cortical superficial cell layers. We did not observe any glial upregulation of A2AR, which was common for both advanced age and chronic neurodegeneration. Taken together, the results imply that the adaptative changes in adenosine signaling occurring in neuronal elements early in life may be responsible for the later prominent glial enhancement in A2AR-mediated adenosine signaling, and neuroinflammation and neurodegeneration, which are the hallmarks of both advanced age and age-associated neurodegenerative diseases.
T2  - Neurochemical Research
T1  - Altered Topographic Distribution and Enhanced Neuronal Expression of Adenosine-Metabolizing Enzymes in Rat Hippocampus and Cortex from Early to late Adulthood
DO  - 10.1007/s11064-022-03557-5
ER  - 

@article{
author = "Dragić, Milorad and Stekić, Anđela and Zeljković, Milica and Zarić Kontić, Marina and Mihajlović, Katarina and Adžić, Marija and Grković, Ivana and Nedeljković, Nadežda",
year = "2022",
abstract = "The present study demonstrates altered topographic distribution and enhanced neuronal expression of major adenosine-metabolizing enzymes, i.e. ecto-5ʹ-nucleotidase (eN) and tissue non-specific alkaline phosphatase (TNAP), as well as adenosine receptor subtype A2A in the hippocampus and cortex of male rats from early to late adulthood (3, 6, 12 and 15 months old males). The significant effect of age was demonstrated for the increase in the activity and the protein expression of eN and TNAP. At 15-m, enzyme histochemistry demonstrated enhanced expression of eN in synapse-rich hippocampal and cortical layers, whereas the upsurge of TNAP was observed in the hippocampal and cortical neuropil, rather than in cells and layers where two enzymes mostly reside in 3-m old brain. Furthermore, a dichotomy in A1R and A2AR expression was demonstrated in the cortex and hippocampus from early to late adulthood. Specifically, a decrease in A1R and enhancement of A2AR expression were demonstrated by immunohistochemistry, the latter being almost exclusively localized in hippocampal pyramidal and cortical superficial cell layers. We did not observe any glial upregulation of A2AR, which was common for both advanced age and chronic neurodegeneration. Taken together, the results imply that the adaptative changes in adenosine signaling occurring in neuronal elements early in life may be responsible for the later prominent glial enhancement in A2AR-mediated adenosine signaling, and neuroinflammation and neurodegeneration, which are the hallmarks of both advanced age and age-associated neurodegenerative diseases.",
journal = "Neurochemical Research",
title = "Altered Topographic Distribution and Enhanced Neuronal Expression of Adenosine-Metabolizing Enzymes in Rat Hippocampus and Cortex from Early to late Adulthood",
doi = "10.1007/s11064-022-03557-5"
}

Dragić, M., Stekić, A., Zeljković, M., Zarić Kontić, M., Mihajlović, K., Adžić, M., Grković, I.,& Nedeljković, N.. (2022). Altered Topographic Distribution and Enhanced Neuronal Expression of Adenosine-Metabolizing Enzymes in Rat Hippocampus and Cortex from Early to late Adulthood. in Neurochemical Research.
https://doi.org/10.1007/s11064-022-03557-5

Dragić M, Stekić A, Zeljković M, Zarić Kontić M, Mihajlović K, Adžić M, Grković I, Nedeljković N. Altered Topographic Distribution and Enhanced Neuronal Expression of Adenosine-Metabolizing Enzymes in Rat Hippocampus and Cortex from Early to late Adulthood. in Neurochemical Research. 2022;.
doi:10.1007/s11064-022-03557-5 .

Dragić, Milorad, Stekić, Anđela, Zeljković, Milica, Zarić Kontić, Marina, Mihajlović, Katarina, Adžić, Marija, Grković, Ivana, Nedeljković, Nadežda, "Altered Topographic Distribution and Enhanced Neuronal Expression of Adenosine-Metabolizing Enzymes in Rat Hippocampus and Cortex from Early to late Adulthood" in Neurochemical Research (2022),
https://doi.org/10.1007/s11064-022-03557-5 . .

TY  - JOUR
AU  - Grković, Ivana
AU  - Mitrović, Nataša
AU  - Dragić, Milorad
AU  - Zarić Kontić, Marina
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10519
AB  - Adenosine 5'-triphosphate (ATP) and other nucleotides and nucleosides, such as adenosine, are versatile signaling molecules involved in many physiological processes and pathological conditions in the nervous system, especially those with an inflammatory component. They can be released from nerve cells, glial cells, and vascular cells into the extracellular space where they exert their function via ionotropic (P2X) or metabotropic (P2Y) receptors. Signaling via extracellular nucleotides and adenosine is regulated by cell-surface located enzymes ectonucleotidases that hydrolyze the nucleotide to the respective nucleoside. This review summarizes a histochemical approach for detection of ectonucleotidase activities in the cryo-sections of brain tissue. The enzyme histochemistry (EHC) might be used as suitable replacement for immunohistochemistry, since it gives information about both localization and activity, thus adding a functional component to a classical histological approach. With this technique, it is possible to visualize spatial distribution and cell-specific localization of ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) and ecto-5'-nucleotidase (eN/CD73) activities during brain development, after different hormonal manipulations, during neurodegeneration, etc. EHC is also suitable for investigation of microglial morphology in different (patho)physiological conditions. Furthermore, the review describes how to quantify EHC results.
T2  - Histology and Histopathology
T1  - Enzyme histochemistry: a useful tool for examining the spatial distribution of brain ectonucleotidases in (patho)physiological conditions
VL  - 37
IS  - 10
SP  - 919
EP  - 936
DO  - 10.14670/HH-18-471
ER  - 

@article{
author = "Grković, Ivana and Mitrović, Nataša and Dragić, Milorad and Zarić Kontić, Marina",
year = "2022",
abstract = "Adenosine 5'-triphosphate (ATP) and other nucleotides and nucleosides, such as adenosine, are versatile signaling molecules involved in many physiological processes and pathological conditions in the nervous system, especially those with an inflammatory component. They can be released from nerve cells, glial cells, and vascular cells into the extracellular space where they exert their function via ionotropic (P2X) or metabotropic (P2Y) receptors. Signaling via extracellular nucleotides and adenosine is regulated by cell-surface located enzymes ectonucleotidases that hydrolyze the nucleotide to the respective nucleoside. This review summarizes a histochemical approach for detection of ectonucleotidase activities in the cryo-sections of brain tissue. The enzyme histochemistry (EHC) might be used as suitable replacement for immunohistochemistry, since it gives information about both localization and activity, thus adding a functional component to a classical histological approach. With this technique, it is possible to visualize spatial distribution and cell-specific localization of ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) and ecto-5'-nucleotidase (eN/CD73) activities during brain development, after different hormonal manipulations, during neurodegeneration, etc. EHC is also suitable for investigation of microglial morphology in different (patho)physiological conditions. Furthermore, the review describes how to quantify EHC results.",
journal = "Histology and Histopathology",
title = "Enzyme histochemistry: a useful tool for examining the spatial distribution of brain ectonucleotidases in (patho)physiological conditions",
volume = "37",
number = "10",
pages = "919-936",
doi = "10.14670/HH-18-471"
}

Grković, I., Mitrović, N., Dragić, M.,& Zarić Kontić, M.. (2022). Enzyme histochemistry: a useful tool for examining the spatial distribution of brain ectonucleotidases in (patho)physiological conditions. in Histology and Histopathology, 37(10), 919-936.
https://doi.org/10.14670/HH-18-471

Grković I, Mitrović N, Dragić M, Zarić Kontić M. Enzyme histochemistry: a useful tool for examining the spatial distribution of brain ectonucleotidases in (patho)physiological conditions. in Histology and Histopathology. 2022;37(10):919-936.
doi:10.14670/HH-18-471 .

Grković, Ivana, Mitrović, Nataša, Dragić, Milorad, Zarić Kontić, Marina, "Enzyme histochemistry: a useful tool for examining the spatial distribution of brain ectonucleotidases in (patho)physiological conditions" in Histology and Histopathology, 37, no. 10 (2022):919-936,
https://doi.org/10.14670/HH-18-471 . .

TY  - JOUR
AU  - Stanojlović, Miloš R.
AU  - Guševac Stojanović, Ivana
AU  - Zarić, Marina
AU  - Martinović, Jelena
AU  - Mitrović, Nataša Lj.
AU  - Grković, Ivana
AU  - Drakulić, Dunja R.
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8742
AB  - Sustained activation of pro-apoptotic signaling due to a sudden and prolonged disturbance of cerebral blood circulation governs the neurodegenerative processes in prefrontal cortex (PFC) of rats whose common carotid arteries are permanently occluded. The adequate neuroprotective therapy should minimize the activation of toxicity pathways and increase the activity of endogenous protective mechanisms. Several neuroprotectants have been proposed, including progesterone (P4). However, the underlying mechanism of its action in PFC following permanent bilateral occlusion of common carotid arteries is not completely investigated. We, thus herein, tested the impact of post-ischemic P4 treatment (1.7 mg/kg for seven consecutive days) on previously reported aberrant neuronal morphology and amount of DNA fragmentation, as well as the expression of progesterone receptors along with the key elements of Akt/Erk/eNOS signal transduction pathway (Bax, Bcl-2, cytochrome C, caspase 3, PARP, and the level of nitric oxide). The obtained results indicate that potential amelioration of histological changes in PFC might be associated with the absence of activation of Bax/caspase 3 signaling cascade and the decline of DNA fragmentation. The study also provides the evidence that P4 treatment in repeated regiment of administration might be effective in neuronal protection against ischemic insult due to re-establishment of the compromised action of Akt/Erk/eNOS-mediated signaling pathway and the upregulation of progesterone receptors. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
T2  - Cellular and Molecular Neurobiology
T1  - Progesterone Protects Prefrontal Cortex in Rat Model of Permanent Bilateral Common Carotid Occlusion via Progesterone Receptors and Akt/Erk/eNOS
VL  - 40
IS  - 5
SP  - 829
EP  - 843
DO  - 10.1007/s10571-019-00777-2
ER  - 

@article{
author = "Stanojlović, Miloš R. and Guševac Stojanović, Ivana and Zarić, Marina and Martinović, Jelena and Mitrović, Nataša Lj. and Grković, Ivana and Drakulić, Dunja R.",
year = "2020",
abstract = "Sustained activation of pro-apoptotic signaling due to a sudden and prolonged disturbance of cerebral blood circulation governs the neurodegenerative processes in prefrontal cortex (PFC) of rats whose common carotid arteries are permanently occluded. The adequate neuroprotective therapy should minimize the activation of toxicity pathways and increase the activity of endogenous protective mechanisms. Several neuroprotectants have been proposed, including progesterone (P4). However, the underlying mechanism of its action in PFC following permanent bilateral occlusion of common carotid arteries is not completely investigated. We, thus herein, tested the impact of post-ischemic P4 treatment (1.7 mg/kg for seven consecutive days) on previously reported aberrant neuronal morphology and amount of DNA fragmentation, as well as the expression of progesterone receptors along with the key elements of Akt/Erk/eNOS signal transduction pathway (Bax, Bcl-2, cytochrome C, caspase 3, PARP, and the level of nitric oxide). The obtained results indicate that potential amelioration of histological changes in PFC might be associated with the absence of activation of Bax/caspase 3 signaling cascade and the decline of DNA fragmentation. The study also provides the evidence that P4 treatment in repeated regiment of administration might be effective in neuronal protection against ischemic insult due to re-establishment of the compromised action of Akt/Erk/eNOS-mediated signaling pathway and the upregulation of progesterone receptors. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.",
journal = "Cellular and Molecular Neurobiology",
title = "Progesterone Protects Prefrontal Cortex in Rat Model of Permanent Bilateral Common Carotid Occlusion via Progesterone Receptors and Akt/Erk/eNOS",
volume = "40",
number = "5",
pages = "829-843",
doi = "10.1007/s10571-019-00777-2"
}

Stanojlović, M. R., Guševac Stojanović, I., Zarić, M., Martinović, J., Mitrović, N. Lj., Grković, I.,& Drakulić, D. R.. (2020). Progesterone Protects Prefrontal Cortex in Rat Model of Permanent Bilateral Common Carotid Occlusion via Progesterone Receptors and Akt/Erk/eNOS. in Cellular and Molecular Neurobiology, 40(5), 829-843.
https://doi.org/10.1007/s10571-019-00777-2

Stanojlović MR, Guševac Stojanović I, Zarić M, Martinović J, Mitrović NL, Grković I, Drakulić DR. Progesterone Protects Prefrontal Cortex in Rat Model of Permanent Bilateral Common Carotid Occlusion via Progesterone Receptors and Akt/Erk/eNOS. in Cellular and Molecular Neurobiology. 2020;40(5):829-843.
doi:10.1007/s10571-019-00777-2 .

Stanojlović, Miloš R., Guševac Stojanović, Ivana, Zarić, Marina, Martinović, Jelena, Mitrović, Nataša Lj., Grković, Ivana, Drakulić, Dunja R., "Progesterone Protects Prefrontal Cortex in Rat Model of Permanent Bilateral Common Carotid Occlusion via Progesterone Receptors and Akt/Erk/eNOS" in Cellular and Molecular Neurobiology, 40, no. 5 (2020):829-843,
https://doi.org/10.1007/s10571-019-00777-2 . .

TY  - THES
AU  - Zarić, Marina
PY  - 2019
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=7338
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:21574/bdef:Content/download
UR  - https://plus.sr.cobiss.net/opac7/bib/1025242546
UR  - http://nardus.mpn.gov.rs/123456789/12179
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8507
AB  - Stanje moždane ishemije/reperfuzije (I/R) karakteristično je za cerebrovaskularnaoboljenja kao što su moţdani udar i tranzitorni ishemijski atak(TIA). Promena signalizacije posredovana N-metil-D-aspartat (NMDA)receptorom ima značajnu ulogu u I/R-uzrokovanom oštećenju, dok jedehidroepiandrosteron (DHEA), pozitvni alosterični modulator NMDAreceptora, najčešće okarakterisan kao neuroprotektivan u tretmanu ishemičnihstanja.U ovoj disertaciji ispitivana je proteinska ekspresija komponentikompleksa NMDA receptora i njegove nishodne signalizacije u hipokampusu iprečeonoj kori muţjaka pacova Wistar soja 24 sata nakon podvezivanja obezajedničke karotidne arterije u trajanju od 15 min i/ili efekat tretmana DHEAprimenjenog 4 sata od hirurške procedure. Praćenje senzo-motorne funkcije iprisustvo infarktnih lezija na presecima celog mozga korišćeno je za validacijuI/R modela za proučavanje blaţih ishemičnih stanja poput TIA. Takođe,izvršeno je ispitivanje efekata I/R i tretmana na histo/morfološkom nivou.Odsustvo senzo-motornih deficita i infarktnih lezija kao i očuvanastruktura tkiva i morfologija neurona u hipokampusu i prečeonoj kori nakonI/R ukazuju na potencijalnu primenu modela u ispitivanju umerenihishemičnih stanja. Region-specifične promene signalnog puta NMDAreceptor/neuralna azot oksid sintaza/azot oksid nakon kratkotrajne I/R govoreu prilog većoj osetljivosti hipokampusa u odnosu na prečeonu koru. EfekatDHEA uočen je isključivo nakon I/R, vraćajući u prečeonoj kori parametare nakontrolnu vrednost, dok u hipokampusu promene Bax/Bcl -2 odnosa ipotencijala mitohondrijske membrane ukazuju na pokretanje pro-apoptotskihdešavanja. Stoga, prethodno okarakterisani neuroprotektivni efekat DHEAtreba dodatno istraţiti.
AB  - Cerebral ischemia/reperfusion (I/R) is characteristic of cerebro-vasculardiseases such as stroke and transient ischemic attack (TIA). Alterations of Nmethyl-D-aspartate (NMDA) receptor-mediated signalling pathway are wellrecognized features of I/R-governed damage, while dehydroepiandrosterone(DHEA), its positive allosteric modulator, has been previously described asneuroprotective and potentially promising for therapy of ischemic conditions.In this doctoral dissertation changes of components of the NMDAreceptor complex and downstream signalling in hippocampus and prefrontalcortex were examined in male Wistar rats 24 h following 15 min bilateralcommon carotid artery occlusion. In addition, effects of 4 h post-surgical DHEAtreatment were investigated. Sensory-motor function and presence of infarctlesions were used to validate suitability of I/R model for studying mildischemic conditions such as TIA. Additionally, effects of I/R and treatmentwere evaluated on histo/morphological level.Absence of sensory-motor deficits and infarct lesions, as well aspreserved tissue structure and overall neuronal morphology in hippocampusand prefrontal cortex following I/R and treatment were detected indicatingsuitability of used I/R model for investigation of mild ischemic states. Regionspecificpostischemic changes of NMDA receptor/neuronal nitric oxidesynthase/nitric oxide following short-term I/R indicate higher sensitivity ofhippocampus compared to prefrontal cortex. DHEA effect was detectedexclusively following I/R, returning the parameters in prefrontal cortex to thecontrol value, while hippocampal Bax/Bcl-2 ratio and mitochondrial membranepotential changes indicate the initiation of pro-apoptotic events. Therefore,previously reported neuroprotective effect of DHEA should be considered withcaution and further investigated.
PB  - Универзитет у Београду, Биолошки факултет
T2  - Универзитет у Београду
T1  - Efekat kratkotrajne moždane ishemije/reperfuzije i tretmana dehidroepiandrosteronom na komponente signalnog puta NMDA receptora u hipokampusu i prečeonoj kori pacova
UR  - https://hdl.handle.net/21.15107/rcub_nardus_12179
ER  - 

@phdthesis{
author = "Zarić, Marina",
year = "2019",
abstract = "Stanje moždane ishemije/reperfuzije (I/R) karakteristično je za cerebrovaskularnaoboljenja kao što su moţdani udar i tranzitorni ishemijski atak(TIA). Promena signalizacije posredovana N-metil-D-aspartat (NMDA)receptorom ima značajnu ulogu u I/R-uzrokovanom oštećenju, dok jedehidroepiandrosteron (DHEA), pozitvni alosterični modulator NMDAreceptora, najčešće okarakterisan kao neuroprotektivan u tretmanu ishemičnihstanja.U ovoj disertaciji ispitivana je proteinska ekspresija komponentikompleksa NMDA receptora i njegove nishodne signalizacije u hipokampusu iprečeonoj kori muţjaka pacova Wistar soja 24 sata nakon podvezivanja obezajedničke karotidne arterije u trajanju od 15 min i/ili efekat tretmana DHEAprimenjenog 4 sata od hirurške procedure. Praćenje senzo-motorne funkcije iprisustvo infarktnih lezija na presecima celog mozga korišćeno je za validacijuI/R modela za proučavanje blaţih ishemičnih stanja poput TIA. Takođe,izvršeno je ispitivanje efekata I/R i tretmana na histo/morfološkom nivou.Odsustvo senzo-motornih deficita i infarktnih lezija kao i očuvanastruktura tkiva i morfologija neurona u hipokampusu i prečeonoj kori nakonI/R ukazuju na potencijalnu primenu modela u ispitivanju umerenihishemičnih stanja. Region-specifične promene signalnog puta NMDAreceptor/neuralna azot oksid sintaza/azot oksid nakon kratkotrajne I/R govoreu prilog većoj osetljivosti hipokampusa u odnosu na prečeonu koru. EfekatDHEA uočen je isključivo nakon I/R, vraćajući u prečeonoj kori parametare nakontrolnu vrednost, dok u hipokampusu promene Bax/Bcl -2 odnosa ipotencijala mitohondrijske membrane ukazuju na pokretanje pro-apoptotskihdešavanja. Stoga, prethodno okarakterisani neuroprotektivni efekat DHEAtreba dodatno istraţiti., Cerebral ischemia/reperfusion (I/R) is characteristic of cerebro-vasculardiseases such as stroke and transient ischemic attack (TIA). Alterations of Nmethyl-D-aspartate (NMDA) receptor-mediated signalling pathway are wellrecognized features of I/R-governed damage, while dehydroepiandrosterone(DHEA), its positive allosteric modulator, has been previously described asneuroprotective and potentially promising for therapy of ischemic conditions.In this doctoral dissertation changes of components of the NMDAreceptor complex and downstream signalling in hippocampus and prefrontalcortex were examined in male Wistar rats 24 h following 15 min bilateralcommon carotid artery occlusion. In addition, effects of 4 h post-surgical DHEAtreatment were investigated. Sensory-motor function and presence of infarctlesions were used to validate suitability of I/R model for studying mildischemic conditions such as TIA. Additionally, effects of I/R and treatmentwere evaluated on histo/morphological level.Absence of sensory-motor deficits and infarct lesions, as well aspreserved tissue structure and overall neuronal morphology in hippocampusand prefrontal cortex following I/R and treatment were detected indicatingsuitability of used I/R model for investigation of mild ischemic states. Regionspecificpostischemic changes of NMDA receptor/neuronal nitric oxidesynthase/nitric oxide following short-term I/R indicate higher sensitivity ofhippocampus compared to prefrontal cortex. DHEA effect was detectedexclusively following I/R, returning the parameters in prefrontal cortex to thecontrol value, while hippocampal Bax/Bcl-2 ratio and mitochondrial membranepotential changes indicate the initiation of pro-apoptotic events. Therefore,previously reported neuroprotective effect of DHEA should be considered withcaution and further investigated.",
publisher = "Универзитет у Београду, Биолошки факултет",
journal = "Универзитет у Београду",
title = "Efekat kratkotrajne moždane ishemije/reperfuzije i tretmana dehidroepiandrosteronom na komponente signalnog puta NMDA receptora u hipokampusu i prečeonoj kori pacova",
url = "https://hdl.handle.net/21.15107/rcub_nardus_12179"
}

Zarić, M.. (2019). Efekat kratkotrajne moždane ishemije/reperfuzije i tretmana dehidroepiandrosteronom na komponente signalnog puta NMDA receptora u hipokampusu i prečeonoj kori pacova. in Универзитет у Београду
Универзитет у Београду, Биолошки факултет..
https://hdl.handle.net/21.15107/rcub_nardus_12179

Zarić M. Efekat kratkotrajne moždane ishemije/reperfuzije i tretmana dehidroepiandrosteronom na komponente signalnog puta NMDA receptora u hipokampusu i prečeonoj kori pacova. in Универзитет у Београду. 2019;.
https://hdl.handle.net/21.15107/rcub_nardus_12179 .

Zarić, Marina, "Efekat kratkotrajne moždane ishemije/reperfuzije i tretmana dehidroepiandrosteronom na komponente signalnog puta NMDA receptora u hipokampusu i prečeonoj kori pacova" in Универзитет у Београду (2019),
https://hdl.handle.net/21.15107/rcub_nardus_12179 .

TY  - JOUR
AU  - Zarić, Marina
AU  - Drakulić, Dunja R.
AU  - Dragić, Milorad
AU  - Guševac Stojanović, Ivana
AU  - Mitrović, Nataša Lj.
AU  - Grković, Ivana
AU  - Martinović, Jelena
PY  - 2019
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0306452219303227
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8203
AB  - Transient ischemic attack (TIA) represents brief neurological dysfunction of vascular origin without detectable infarction. Despite major clinical relevance characterization of post-TIA molecular changes using appropriate experimental model is lacking and no therapeutic agent has been established yet. Neurosteroid dehydroepiandrosterone (DHEA) arose as one of the candidates for cerebral ischemia treatment but its effects on TIA-like condition remain unknown. Seeking an animal model applicable for investigation of molecular alterations in mild ischemic conditions such as TIA, 15-min bilateral common carotid artery occlusion with 24-h reperfusion was performed to induce ischemia/ reperfusion (I/R) injury in adult male Wistar rats. Additionally, effects of 4-h post-operative DHEA treatment (20 mg/kg) were investigated in physiological and I/R conditions in hippocampus (HIP) and prefrontal cortex (PFC). The study revealed absence of sensorimotor deficits, cerebral infarcts and neurodegeneration along with preserved HIP and PFC overall neuronal morphology and unaltered malondialdehyde and reduced glutathione level following I/R and/or DHEA treatment. I/R induced nitric oxide burst in HIP and PFC was accompanied with increased neuronal nitric oxide synthase protein level exclusively in HIP. DHEA had no effects in physiological conditions, while increase of Bax/Bcl2 ratio and dissipation of mitochondrial membrane potential in treated I/R group suggested DHEA-mediated exacerbation of post-ischemic changes that might lead to pro-apoptotic events in HIP. Interestingly, DHEA restored I/R-induced NO to the control level in PFC. Obtained results indicated that I/R may serve as an appropriate model for investigation of molecular changes and treatment outcome following mild ischemic conditions such as TIA. © 2019 Elsevier Ltd
T2  - Neuroscience
T1  - Molecular Alterations and Effects of Acute Dehydroepiandrosterone Treatment Following Brief Bilateral Common Carotid Artery Occlusion: Relevance to Transient Ischemic Attack
VL  - 410
SP  - 128
EP  - 139
DO  - 10.1016/j.neuroscience.2019.05.006
ER  - 

@article{
author = "Zarić, Marina and Drakulić, Dunja R. and Dragić, Milorad and Guševac Stojanović, Ivana and Mitrović, Nataša Lj. and Grković, Ivana and Martinović, Jelena",
year = "2019",
abstract = "Transient ischemic attack (TIA) represents brief neurological dysfunction of vascular origin without detectable infarction. Despite major clinical relevance characterization of post-TIA molecular changes using appropriate experimental model is lacking and no therapeutic agent has been established yet. Neurosteroid dehydroepiandrosterone (DHEA) arose as one of the candidates for cerebral ischemia treatment but its effects on TIA-like condition remain unknown. Seeking an animal model applicable for investigation of molecular alterations in mild ischemic conditions such as TIA, 15-min bilateral common carotid artery occlusion with 24-h reperfusion was performed to induce ischemia/ reperfusion (I/R) injury in adult male Wistar rats. Additionally, effects of 4-h post-operative DHEA treatment (20 mg/kg) were investigated in physiological and I/R conditions in hippocampus (HIP) and prefrontal cortex (PFC). The study revealed absence of sensorimotor deficits, cerebral infarcts and neurodegeneration along with preserved HIP and PFC overall neuronal morphology and unaltered malondialdehyde and reduced glutathione level following I/R and/or DHEA treatment. I/R induced nitric oxide burst in HIP and PFC was accompanied with increased neuronal nitric oxide synthase protein level exclusively in HIP. DHEA had no effects in physiological conditions, while increase of Bax/Bcl2 ratio and dissipation of mitochondrial membrane potential in treated I/R group suggested DHEA-mediated exacerbation of post-ischemic changes that might lead to pro-apoptotic events in HIP. Interestingly, DHEA restored I/R-induced NO to the control level in PFC. Obtained results indicated that I/R may serve as an appropriate model for investigation of molecular changes and treatment outcome following mild ischemic conditions such as TIA. © 2019 Elsevier Ltd",
journal = "Neuroscience",
title = "Molecular Alterations and Effects of Acute Dehydroepiandrosterone Treatment Following Brief Bilateral Common Carotid Artery Occlusion: Relevance to Transient Ischemic Attack",
volume = "410",
pages = "128-139",
doi = "10.1016/j.neuroscience.2019.05.006"
}

Zarić, M., Drakulić, D. R., Dragić, M., Guševac Stojanović, I., Mitrović, N. Lj., Grković, I.,& Martinović, J.. (2019). Molecular Alterations and Effects of Acute Dehydroepiandrosterone Treatment Following Brief Bilateral Common Carotid Artery Occlusion: Relevance to Transient Ischemic Attack. in Neuroscience, 410, 128-139.
https://doi.org/10.1016/j.neuroscience.2019.05.006

Zarić M, Drakulić DR, Dragić M, Guševac Stojanović I, Mitrović NL, Grković I, Martinović J. Molecular Alterations and Effects of Acute Dehydroepiandrosterone Treatment Following Brief Bilateral Common Carotid Artery Occlusion: Relevance to Transient Ischemic Attack. in Neuroscience. 2019;410:128-139.
doi:10.1016/j.neuroscience.2019.05.006 .

Zarić, Marina, Drakulić, Dunja R., Dragić, Milorad, Guševac Stojanović, Ivana, Mitrović, Nataša Lj., Grković, Ivana, Martinović, Jelena, "Molecular Alterations and Effects of Acute Dehydroepiandrosterone Treatment Following Brief Bilateral Common Carotid Artery Occlusion: Relevance to Transient Ischemic Attack" in Neuroscience, 410 (2019):128-139,
https://doi.org/10.1016/j.neuroscience.2019.05.006 . .

TY  - JOUR
AU  - Dragić, Milorad
AU  - Zarić, Marina
AU  - Mitrović, Nataša Lj.
AU  - Nedeljković, Nadežda
AU  - Grković, Ivana
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8489
AB  - Enzyme histochemistry is a valuable histological method which provides a connection between morphology, activity, and spatial localization of investigated enzymes. Even though the method relies purely on arbitrary evaluations performed by the human eye, it is still wildly accepted and used in histo(patho)logy. Texture analysis emerged as an excellent tool for image quantification of subtle differences reflected in both spatial discrepancies and gray level values of pixels. The current study of texture analysis utilizes the gray-level co-occurrence matrix as a method for quantification of differences between ecto-5′-nucleotidase activities in healthy hippocampal tissue and tissue with marked neurodegeneration. We used the angular second moment, contrast (CON), correlation, inverse difference moment (INV), and entropy for texture analysis and receiver operating characteristic analysis with immunoblot and qualitative assessment of enzyme histochemistry as a validation. Our results strongly argue that co-occurrence matrix analysis could be used for the determination of fine differences in the enzyme activities with the possibility to ascribe those differences to regions or specific cell types. In addition, it emerged that INV and CON are especially useful parameters for this type of enzyme histochemistry analysis. We concluded that texture analysis is a reliable method for quantification of this descriptive technique, thus removing biases and adding it a quantitative dimension.
T2  - Microscopy and Microanalysis
T1  - Application of Gray Level Co-Occurrence Matrix Analysis as a New Method for Enzyme Histochemistry Quantification
VL  - 25
IS  - 3
SP  - 690
EP  - 698
DO  - 10.1017/S1431927618016306
ER  - 

@article{
author = "Dragić, Milorad and Zarić, Marina and Mitrović, Nataša Lj. and Nedeljković, Nadežda and Grković, Ivana",
year = "2019",
abstract = "Enzyme histochemistry is a valuable histological method which provides a connection between morphology, activity, and spatial localization of investigated enzymes. Even though the method relies purely on arbitrary evaluations performed by the human eye, it is still wildly accepted and used in histo(patho)logy. Texture analysis emerged as an excellent tool for image quantification of subtle differences reflected in both spatial discrepancies and gray level values of pixels. The current study of texture analysis utilizes the gray-level co-occurrence matrix as a method for quantification of differences between ecto-5′-nucleotidase activities in healthy hippocampal tissue and tissue with marked neurodegeneration. We used the angular second moment, contrast (CON), correlation, inverse difference moment (INV), and entropy for texture analysis and receiver operating characteristic analysis with immunoblot and qualitative assessment of enzyme histochemistry as a validation. Our results strongly argue that co-occurrence matrix analysis could be used for the determination of fine differences in the enzyme activities with the possibility to ascribe those differences to regions or specific cell types. In addition, it emerged that INV and CON are especially useful parameters for this type of enzyme histochemistry analysis. We concluded that texture analysis is a reliable method for quantification of this descriptive technique, thus removing biases and adding it a quantitative dimension.",
journal = "Microscopy and Microanalysis",
title = "Application of Gray Level Co-Occurrence Matrix Analysis as a New Method for Enzyme Histochemistry Quantification",
volume = "25",
number = "3",
pages = "690-698",
doi = "10.1017/S1431927618016306"
}

Dragić, M., Zarić, M., Mitrović, N. Lj., Nedeljković, N.,& Grković, I.. (2019). Application of Gray Level Co-Occurrence Matrix Analysis as a New Method for Enzyme Histochemistry Quantification. in Microscopy and Microanalysis, 25(3), 690-698.
https://doi.org/10.1017/S1431927618016306

Dragić M, Zarić M, Mitrović NL, Nedeljković N, Grković I. Application of Gray Level Co-Occurrence Matrix Analysis as a New Method for Enzyme Histochemistry Quantification. in Microscopy and Microanalysis. 2019;25(3):690-698.
doi:10.1017/S1431927618016306 .

Dragić, Milorad, Zarić, Marina, Mitrović, Nataša Lj., Nedeljković, Nadežda, Grković, Ivana, "Application of Gray Level Co-Occurrence Matrix Analysis as a New Method for Enzyme Histochemistry Quantification" in Microscopy and Microanalysis, 25, no. 3 (2019):690-698,
https://doi.org/10.1017/S1431927618016306 . .

TY  - JOUR
AU  - Mitrović, Nataša Lj.
AU  - Dragić, Milorad
AU  - Zarić, Marina
AU  - Drakulić, Dunja R.
AU  - Nedeljković, Nadežda
AU  - Grković, Ivana
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8497
AB  - Extracellular adenine nucleotides and nucleosides, such as adenosine-5'-triphosphate (ATP) and adenosine, are among least investigated signaling factors that participate in 17β-estradiol (E2)-mediated synaptic rearrangements in rodent hippocampus. Their levels in the extrasynaptic space are tightly controlled by ecto-nucleoside triphosphate diphosphohydrolases1-3 (NTPDase1-3)/ecto-5'-nucleotidase (eN) enzyme chain. Therefore, the aim of the present study was to get closer insight in the E2-induced decrease in NTPDase and eN activity in the hippocampal synaptic compartment of male rats and to identify estradiol receptors (ERs i.e. ERα, ERβ or GPER1) responsible for the observed effects of E2. In this study we show indiscriminate participation of estradiol receptor α (ERα), -β (ERβ) and G- protein coupled estrogen receptor 1 (GPER1) in the mediation of E2 actions in hippocampal synaptosomes of male rats. Synaptic NTPDase1-3 activities are modulated only through activation of ERβ, while activation of ERα, -β and/or non-classical GPER1 decreases synaptic eN activity. Since both ATP and adenosine function as neuromodulators in the hippocampal networks, influencing its function, profound knowledge of mechanisms by which ectonucleotidases are regulated/modulated is of great importance. © 2019 Elsevier B.V.
T2  - Neuroscience Letters
T1  - Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats
VL  - 712
SP  - 134474
DO  - 10.1016/j.neulet.2019.134474
ER  - 

@article{
author = "Mitrović, Nataša Lj. and Dragić, Milorad and Zarić, Marina and Drakulić, Dunja R. and Nedeljković, Nadežda and Grković, Ivana",
year = "2019",
abstract = "Extracellular adenine nucleotides and nucleosides, such as adenosine-5'-triphosphate (ATP) and adenosine, are among least investigated signaling factors that participate in 17β-estradiol (E2)-mediated synaptic rearrangements in rodent hippocampus. Their levels in the extrasynaptic space are tightly controlled by ecto-nucleoside triphosphate diphosphohydrolases1-3 (NTPDase1-3)/ecto-5'-nucleotidase (eN) enzyme chain. Therefore, the aim of the present study was to get closer insight in the E2-induced decrease in NTPDase and eN activity in the hippocampal synaptic compartment of male rats and to identify estradiol receptors (ERs i.e. ERα, ERβ or GPER1) responsible for the observed effects of E2. In this study we show indiscriminate participation of estradiol receptor α (ERα), -β (ERβ) and G- protein coupled estrogen receptor 1 (GPER1) in the mediation of E2 actions in hippocampal synaptosomes of male rats. Synaptic NTPDase1-3 activities are modulated only through activation of ERβ, while activation of ERα, -β and/or non-classical GPER1 decreases synaptic eN activity. Since both ATP and adenosine function as neuromodulators in the hippocampal networks, influencing its function, profound knowledge of mechanisms by which ectonucleotidases are regulated/modulated is of great importance. © 2019 Elsevier B.V.",
journal = "Neuroscience Letters",
title = "Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats",
volume = "712",
pages = "134474",
doi = "10.1016/j.neulet.2019.134474"
}

Mitrović, N. Lj., Dragić, M., Zarić, M., Drakulić, D. R., Nedeljković, N.,& Grković, I.. (2019). Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats. in Neuroscience Letters, 712, 134474.
https://doi.org/10.1016/j.neulet.2019.134474

Mitrović NL, Dragić M, Zarić M, Drakulić DR, Nedeljković N, Grković I. Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats. in Neuroscience Letters. 2019;712:134474.
doi:10.1016/j.neulet.2019.134474 .

Mitrović, Nataša Lj., Dragić, Milorad, Zarić, Marina, Drakulić, Dunja R., Nedeljković, Nadežda, Grković, Ivana, "Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats" in Neuroscience Letters, 712 (2019):134474,
https://doi.org/10.1016/j.neulet.2019.134474 . .

TY  - JOUR
AU  - Dragić, Milorad
AU  - Zarić, Marina
AU  - Mitrović, Nataša Lj.
AU  - Nedeljković, Nadežda
AU  - Grković, Ivana
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8647
AB  - Astrocytes comprise a heterogenic group of glial cells, which perform homeostatic functions in the central nervous system. These cells react to all kind of insults by changing the morphology and function that result in a transition from the quiescent to a reactive phenotype. Trimethyltin (TMT) intoxication, which reproduces pathological events in the hippocampus similar to those associated with seizures and cognitive decline, has been proven as a useful model for studying responses of the glial cells to neurodegeneration. In the present study, we have explored morphological varieties of astrocytes in the hippocampal subregions of ovariectomized female rats exposed to TMT. We have demonstrated an early loss of neurons in CA1 and DG subfields. Distinct morphotypes of protoplasmic astrocytes observed in CA1/CA3 and the hilus of control animals developed different responses to TMT intoxication, as assessed by GFAP-immunohistochemistry. In CA1 subregion, GFAP+ astrocytes preserved their domain organization and responded with typical hypertrophy, while the hilar GFAP+ astrocytes developed atrophy-like phenotype and increased expression of vimentin and nestin 7 days after the exposure. Both reactive and atrophied-like astrocytes expressed Kir4.1 in CA1/CA3 and the hilus of DG, respectively, indicating that these cells did not change their potential for normal activity at this time point of pathology. Together, the results demonstrate the persistence of two protoplasmic morphotypes of astrocytes, with distinct appearance, function, and fate after TMT-induced neurodegeneration, suggesting their pleiotropic roles in the hippocampal response to neurodegeneration. © 2019 IBRO
T2  - Neuroscience
T1  - Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication
VL  - 423
SP  - 38
EP  - 54
DO  - 10.1016/j.neuroscience.2019.10.022
ER  - 

@article{
author = "Dragić, Milorad and Zarić, Marina and Mitrović, Nataša Lj. and Nedeljković, Nadežda and Grković, Ivana",
year = "2019",
abstract = "Astrocytes comprise a heterogenic group of glial cells, which perform homeostatic functions in the central nervous system. These cells react to all kind of insults by changing the morphology and function that result in a transition from the quiescent to a reactive phenotype. Trimethyltin (TMT) intoxication, which reproduces pathological events in the hippocampus similar to those associated with seizures and cognitive decline, has been proven as a useful model for studying responses of the glial cells to neurodegeneration. In the present study, we have explored morphological varieties of astrocytes in the hippocampal subregions of ovariectomized female rats exposed to TMT. We have demonstrated an early loss of neurons in CA1 and DG subfields. Distinct morphotypes of protoplasmic astrocytes observed in CA1/CA3 and the hilus of control animals developed different responses to TMT intoxication, as assessed by GFAP-immunohistochemistry. In CA1 subregion, GFAP+ astrocytes preserved their domain organization and responded with typical hypertrophy, while the hilar GFAP+ astrocytes developed atrophy-like phenotype and increased expression of vimentin and nestin 7 days after the exposure. Both reactive and atrophied-like astrocytes expressed Kir4.1 in CA1/CA3 and the hilus of DG, respectively, indicating that these cells did not change their potential for normal activity at this time point of pathology. Together, the results demonstrate the persistence of two protoplasmic morphotypes of astrocytes, with distinct appearance, function, and fate after TMT-induced neurodegeneration, suggesting their pleiotropic roles in the hippocampal response to neurodegeneration. © 2019 IBRO",
journal = "Neuroscience",
title = "Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication",
volume = "423",
pages = "38-54",
doi = "10.1016/j.neuroscience.2019.10.022"
}

Dragić, M., Zarić, M., Mitrović, N. Lj., Nedeljković, N.,& Grković, I.. (2019). Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication. in Neuroscience, 423, 38-54.
https://doi.org/10.1016/j.neuroscience.2019.10.022

Dragić M, Zarić M, Mitrović NL, Nedeljković N, Grković I. Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication. in Neuroscience. 2019;423:38-54.
doi:10.1016/j.neuroscience.2019.10.022 .

Dragić, Milorad, Zarić, Marina, Mitrović, Nataša Lj., Nedeljković, Nadežda, Grković, Ivana, "Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication" in Neuroscience, 423 (2019):38-54,
https://doi.org/10.1016/j.neuroscience.2019.10.022 . .

TY  - JOUR
AU  - Zarić, Marina
AU  - Drakulić, Dunja R.
AU  - Guševac Stojanović, Ivana
AU  - Mitrović, Nataša Lj.
AU  - Grković, Ivana
AU  - Martinović, Jelena
PY  - 2018
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7626
AB  - Excessive glutamate efflux and N-methyl-D-aspartate receptor (NMDAR) over -activation represent wellknown hallmarks of cerebral ischemia/reperfusion (I/R) injury, still, expression of proteins involved in this aspect of I/R pathophysiology show inconsistent data. Neurosteroid dehydroepiandrosterone (DHEA) has been proposed as potent NMDAR modulator, but its influence on I/R-induced changes up to date remains questionable. Therefore, I/R-governed alteration of vesicular glutamate transporter 1 (vGluT1), synaptic NMDAR subunit composition, postsynaptic density protein 95 (PSD-95) and neuronal morphology alone or following DHEA treatment were examined. For that purpose, adult male Wistar rats were treated with a single dose of vehicle or DHEA (20 mg/kg i.p.) 4 h following sham operation or 15 min bilateral common carotid artery occlusion. Western blot was used for analyses of synaptic protein expressions in hippocampus and prefrontal cortex, while neuronal morphology was assessed using Nissl staining. Regional -specific postischemic changes were detected on protein level i.e. signs of neuronal damage in CA1 area was accompanied with hippocampal vGluT1, NR1, NR2B enhancement and PSD-95 decrement, while histological changes observed in layer III were associated with decreased NR1 subunit in prefrontal cortex. Under physiological conditions DHEA had no effect on protein and histological appearance, while in ischemic milieu it restored hippocampal PSD-95 and NR1 in prefrontal cortex to the control level. Along with intact neurons, ones characterized by morphology observed in I/R group were also present. Future studies involving NMDAR-related intracellular signaling and immunohistochemical analysis will reveal precise effects of I/R and DHEA treatment in selected brain regions. (C) 2018 Elsevier B.V. All rights reserved.
T2  - Brain Research
T1  - Regional-specific effects of cerebral ischemia/reperfusion and dehydroepiandrosterone on synaptic NMDAR/PSD-95 complex in male Wistar rats
VL  - 1688
SP  - 73
EP  - 80
DO  - 10.1016/j.brainres.2018.03.023
ER  - 

@article{
author = "Zarić, Marina and Drakulić, Dunja R. and Guševac Stojanović, Ivana and Mitrović, Nataša Lj. and Grković, Ivana and Martinović, Jelena",
year = "2018",
abstract = "Excessive glutamate efflux and N-methyl-D-aspartate receptor (NMDAR) over -activation represent wellknown hallmarks of cerebral ischemia/reperfusion (I/R) injury, still, expression of proteins involved in this aspect of I/R pathophysiology show inconsistent data. Neurosteroid dehydroepiandrosterone (DHEA) has been proposed as potent NMDAR modulator, but its influence on I/R-induced changes up to date remains questionable. Therefore, I/R-governed alteration of vesicular glutamate transporter 1 (vGluT1), synaptic NMDAR subunit composition, postsynaptic density protein 95 (PSD-95) and neuronal morphology alone or following DHEA treatment were examined. For that purpose, adult male Wistar rats were treated with a single dose of vehicle or DHEA (20 mg/kg i.p.) 4 h following sham operation or 15 min bilateral common carotid artery occlusion. Western blot was used for analyses of synaptic protein expressions in hippocampus and prefrontal cortex, while neuronal morphology was assessed using Nissl staining. Regional -specific postischemic changes were detected on protein level i.e. signs of neuronal damage in CA1 area was accompanied with hippocampal vGluT1, NR1, NR2B enhancement and PSD-95 decrement, while histological changes observed in layer III were associated with decreased NR1 subunit in prefrontal cortex. Under physiological conditions DHEA had no effect on protein and histological appearance, while in ischemic milieu it restored hippocampal PSD-95 and NR1 in prefrontal cortex to the control level. Along with intact neurons, ones characterized by morphology observed in I/R group were also present. Future studies involving NMDAR-related intracellular signaling and immunohistochemical analysis will reveal precise effects of I/R and DHEA treatment in selected brain regions. (C) 2018 Elsevier B.V. All rights reserved.",
journal = "Brain Research",
title = "Regional-specific effects of cerebral ischemia/reperfusion and dehydroepiandrosterone on synaptic NMDAR/PSD-95 complex in male Wistar rats",
volume = "1688",
pages = "73-80",
doi = "10.1016/j.brainres.2018.03.023"
}

Zarić, M., Drakulić, D. R., Guševac Stojanović, I., Mitrović, N. Lj., Grković, I.,& Martinović, J.. (2018). Regional-specific effects of cerebral ischemia/reperfusion and dehydroepiandrosterone on synaptic NMDAR/PSD-95 complex in male Wistar rats. in Brain Research, 1688, 73-80.
https://doi.org/10.1016/j.brainres.2018.03.023

Zarić M, Drakulić DR, Guševac Stojanović I, Mitrović NL, Grković I, Martinović J. Regional-specific effects of cerebral ischemia/reperfusion and dehydroepiandrosterone on synaptic NMDAR/PSD-95 complex in male Wistar rats. in Brain Research. 2018;1688:73-80.
doi:10.1016/j.brainres.2018.03.023 .

Zarić, Marina, Drakulić, Dunja R., Guševac Stojanović, Ivana, Mitrović, Nataša Lj., Grković, Ivana, Martinović, Jelena, "Regional-specific effects of cerebral ischemia/reperfusion and dehydroepiandrosterone on synaptic NMDAR/PSD-95 complex in male Wistar rats" in Brain Research, 1688 (2018):73-80,
https://doi.org/10.1016/j.brainres.2018.03.023 . .

TY  - JOUR
AU  - Petrović, Nina
AU  - Sami, Ahmad
AU  - Martinović, Jelena
AU  - Zarić, Marina
AU  - Nakashidze, Irina
AU  - Lukić, Silvana
AU  - Jovanović-Ćupić, Snežana P.
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1805
AB  - Background: Breast carcinomas (BC) belong to a heterogeneous group of malignant diseases. Correct categorization of BC based on molecular biomarkers has a very important role in deciding the proper course of therapy for each patient. It has been already shown that the decrease of TIMP metalloproteinase inhibitor 3 (TIMP-3) together with overexpression of microRNA-21 (miR-21) might be involved in the process of BC invasion. This is the first study that examined relationship among miR-21, TIMP-3 mRNA and TIPM-3 protein levels in BC groups formed according to invasiveness. Methods: In this study, we used 46 breast cancer samples. Estrogen and progesterone receptor (ER, PR) protein levels were evaluated by immunohistochemistry (IHC) method. TIMP-3 mRNA expression was examined by two-step real-time quantitative PCR (qRT-PCR). Western blot analysis was performed for 16 samples. Results: Statistically significant differences in TIMP-3 expression levels between invasive groups were discovered in ER positive (ER+) (p = 0.015), Her-2 negative (p = 0.026) subgroups, and patients without lymph-node metastasis (p = 0.039). Interestingly, significant positive correlation was detected between miR-21 and TIMP-3 mRNA levels (P LT 0.001, p = 0.949) in the group of in situ tumors. TIMP-3 mRNA expression levels highly negatively correlated with levels of miR-21 in PR + invasive BCs (p = 0.007, p = -0.641). TIMP-3 protein levels negatively correlated with miR-21 levels in pure invasive BCs. Conclusion: These data suggest that signaling pathways involved in formation and progression of BCs in groups formed according to invasiveness might be different. Our findings propose that TIMP-3 mRNA expression levels could be significant prognostic parameter, but within specific BC subtypes.
T2  - Pathology Research and Practice
T1  - TIMP-3 mRNA expression levels positively correlates with levels of miR-21 in in situ BC and negatively in PR positive invasive BC
VL  - 213
IS  - 10
SP  - 1264
EP  - 1270
DO  - 10.1016/j.prp.2017.08.012
ER  - 

@article{
author = "Petrović, Nina and Sami, Ahmad and Martinović, Jelena and Zarić, Marina and Nakashidze, Irina and Lukić, Silvana and Jovanović-Ćupić, Snežana P.",
year = "2017",
abstract = "Background: Breast carcinomas (BC) belong to a heterogeneous group of malignant diseases. Correct categorization of BC based on molecular biomarkers has a very important role in deciding the proper course of therapy for each patient. It has been already shown that the decrease of TIMP metalloproteinase inhibitor 3 (TIMP-3) together with overexpression of microRNA-21 (miR-21) might be involved in the process of BC invasion. This is the first study that examined relationship among miR-21, TIMP-3 mRNA and TIPM-3 protein levels in BC groups formed according to invasiveness. Methods: In this study, we used 46 breast cancer samples. Estrogen and progesterone receptor (ER, PR) protein levels were evaluated by immunohistochemistry (IHC) method. TIMP-3 mRNA expression was examined by two-step real-time quantitative PCR (qRT-PCR). Western blot analysis was performed for 16 samples. Results: Statistically significant differences in TIMP-3 expression levels between invasive groups were discovered in ER positive (ER+) (p = 0.015), Her-2 negative (p = 0.026) subgroups, and patients without lymph-node metastasis (p = 0.039). Interestingly, significant positive correlation was detected between miR-21 and TIMP-3 mRNA levels (P LT 0.001, p = 0.949) in the group of in situ tumors. TIMP-3 mRNA expression levels highly negatively correlated with levels of miR-21 in PR + invasive BCs (p = 0.007, p = -0.641). TIMP-3 protein levels negatively correlated with miR-21 levels in pure invasive BCs. Conclusion: These data suggest that signaling pathways involved in formation and progression of BCs in groups formed according to invasiveness might be different. Our findings propose that TIMP-3 mRNA expression levels could be significant prognostic parameter, but within specific BC subtypes.",
journal = "Pathology Research and Practice",
title = "TIMP-3 mRNA expression levels positively correlates with levels of miR-21 in in situ BC and negatively in PR positive invasive BC",
volume = "213",
number = "10",
pages = "1264-1270",
doi = "10.1016/j.prp.2017.08.012"
}

Petrović, N., Sami, A., Martinović, J., Zarić, M., Nakashidze, I., Lukić, S.,& Jovanović-Ćupić, S. P.. (2017). TIMP-3 mRNA expression levels positively correlates with levels of miR-21 in in situ BC and negatively in PR positive invasive BC. in Pathology Research and Practice, 213(10), 1264-1270.
https://doi.org/10.1016/j.prp.2017.08.012

Petrović N, Sami A, Martinović J, Zarić M, Nakashidze I, Lukić S, Jovanović-Ćupić SP. TIMP-3 mRNA expression levels positively correlates with levels of miR-21 in in situ BC and negatively in PR positive invasive BC. in Pathology Research and Practice. 2017;213(10):1264-1270.
doi:10.1016/j.prp.2017.08.012 .

Petrović, Nina, Sami, Ahmad, Martinović, Jelena, Zarić, Marina, Nakashidze, Irina, Lukić, Silvana, Jovanović-Ćupić, Snežana P., "TIMP-3 mRNA expression levels positively correlates with levels of miR-21 in in situ BC and negatively in PR positive invasive BC" in Pathology Research and Practice, 213, no. 10 (2017):1264-1270,
https://doi.org/10.1016/j.prp.2017.08.012 . .

TY  - JOUR
AU  - Mitrović, Nataša Lj.
AU  - Zarić, Marina
AU  - Drakulić, Dunja R.
AU  - Martinović, Jelena
AU  - Sevigny, Jean
AU  - Stanojlović, Miloš R.
AU  - Nedeljković, Nadežda
AU  - Grković, Ivana
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1459
AB  - 17 beta-Estradiol (E2) rapidly, by binding to membrane estrogen receptors, activates cell signaling cascades which induce formation of new dendritic spines in the hippocampus of males as in females, but the interaction with other metabolic processes, such as extracellular adenine nucleotides metabolism, are currently unknown. Extracellular adenine nucleotides play significant roles, controlling excitatory glutamatergic synapses and development of neural circuits and synaptic plasticity. Their precise regulation in the synaptic cleft is tightly controlled by ecto-nucleoside triphosphate diphosphohydrolase (NTPDase)/ecto-5-nucleotidase (eN) enzyme chain. Therefore, we sought to clarify whether a single systemic injection of E2 in male rats is accompanied by changes in the expression of the pre- and postsynaptic proteins and downstream kinases linked to E2-induced synaptic rearrangement as well as alterations in NTPDase/eN pathway in the hippocampal synaptosomes. Obtained data showed activation of mammalian target of rapamycin and upregulation of key synaptic proteins necessary for spine formation, 24 h after systemic E2 administration. In E2-mediated conditions, we found downregulation of NTPDase1 and NTPDase2 and attenuation of adenine nucleotide hydrolysis by NTPDase/eN enzyme chain, without changes in NTPDase3 properties and augmentation of synaptic tissue-nonspecific alkaline phosphatase (TNAP) activity. Despite reduced NTPDase activities, increased TNAP activity probably prevents toxic accumulation of ATP in the extracellular milieu and also hydrolyzes accumulated ADP due to unchanged NTPDase3 activity. Thus, our initial evaluation supports idea of specific roles of different ectonucleotidases and their coordinated actions in E2-mediated spine remodeling and maintenance.
T2  - Journal of Molecular Neuroscience
T1  - 17 beta-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes
VL  - 61
IS  - 3
SP  - 412
EP  - 422
DO  - 10.1007/s12031-016-0877-6
ER  - 

@article{
author = "Mitrović, Nataša Lj. and Zarić, Marina and Drakulić, Dunja R. and Martinović, Jelena and Sevigny, Jean and Stanojlović, Miloš R. and Nedeljković, Nadežda and Grković, Ivana",
year = "2017",
abstract = "17 beta-Estradiol (E2) rapidly, by binding to membrane estrogen receptors, activates cell signaling cascades which induce formation of new dendritic spines in the hippocampus of males as in females, but the interaction with other metabolic processes, such as extracellular adenine nucleotides metabolism, are currently unknown. Extracellular adenine nucleotides play significant roles, controlling excitatory glutamatergic synapses and development of neural circuits and synaptic plasticity. Their precise regulation in the synaptic cleft is tightly controlled by ecto-nucleoside triphosphate diphosphohydrolase (NTPDase)/ecto-5-nucleotidase (eN) enzyme chain. Therefore, we sought to clarify whether a single systemic injection of E2 in male rats is accompanied by changes in the expression of the pre- and postsynaptic proteins and downstream kinases linked to E2-induced synaptic rearrangement as well as alterations in NTPDase/eN pathway in the hippocampal synaptosomes. Obtained data showed activation of mammalian target of rapamycin and upregulation of key synaptic proteins necessary for spine formation, 24 h after systemic E2 administration. In E2-mediated conditions, we found downregulation of NTPDase1 and NTPDase2 and attenuation of adenine nucleotide hydrolysis by NTPDase/eN enzyme chain, without changes in NTPDase3 properties and augmentation of synaptic tissue-nonspecific alkaline phosphatase (TNAP) activity. Despite reduced NTPDase activities, increased TNAP activity probably prevents toxic accumulation of ATP in the extracellular milieu and also hydrolyzes accumulated ADP due to unchanged NTPDase3 activity. Thus, our initial evaluation supports idea of specific roles of different ectonucleotidases and their coordinated actions in E2-mediated spine remodeling and maintenance.",
journal = "Journal of Molecular Neuroscience",
title = "17 beta-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes",
volume = "61",
number = "3",
pages = "412-422",
doi = "10.1007/s12031-016-0877-6"
}

Mitrović, N. Lj., Zarić, M., Drakulić, D. R., Martinović, J., Sevigny, J., Stanojlović, M. R., Nedeljković, N.,& Grković, I.. (2017). 17 beta-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes. in Journal of Molecular Neuroscience, 61(3), 412-422.
https://doi.org/10.1007/s12031-016-0877-6

Mitrović NL, Zarić M, Drakulić DR, Martinović J, Sevigny J, Stanojlović MR, Nedeljković N, Grković I. 17 beta-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes. in Journal of Molecular Neuroscience. 2017;61(3):412-422.
doi:10.1007/s12031-016-0877-6 .

Mitrović, Nataša Lj., Zarić, Marina, Drakulić, Dunja R., Martinović, Jelena, Sevigny, Jean, Stanojlović, Miloš R., Nedeljković, Nadežda, Grković, Ivana, "17 beta-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes" in Journal of Molecular Neuroscience, 61, no. 3 (2017):412-422,
https://doi.org/10.1007/s12031-016-0877-6 . .

TY  - JOUR
AU  - Mitrović, Nataša Lj.
AU  - Zarić, Marina
AU  - Drakulić, Dunja R.
AU  - Martinović, Jelena
AU  - Sevigny, Jean
AU  - Stanojlović, Miloš R.
AU  - Nedeljković, Nadežda
AU  - Grković, Ivana
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1460
T2  - Journal of Molecular Neuroscience
T1  - Erratum to: 17 beta-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes
VL  - 61
IS  - 3
SP  - 423
EP  - 424
DO  - 10.1007/s12031-016-0879-4
ER  - 

@article{
author = "Mitrović, Nataša Lj. and Zarić, Marina and Drakulić, Dunja R. and Martinović, Jelena and Sevigny, Jean and Stanojlović, Miloš R. and Nedeljković, Nadežda and Grković, Ivana",
year = "2017",
journal = "Journal of Molecular Neuroscience",
title = "Erratum to: 17 beta-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes",
volume = "61",
number = "3",
pages = "423-424",
doi = "10.1007/s12031-016-0879-4"
}

Mitrović, N. Lj., Zarić, M., Drakulić, D. R., Martinović, J., Sevigny, J., Stanojlović, M. R., Nedeljković, N.,& Grković, I.. (2017). Erratum to: 17 beta-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes. in Journal of Molecular Neuroscience, 61(3), 423-424.
https://doi.org/10.1007/s12031-016-0879-4

Mitrović NL, Zarić M, Drakulić DR, Martinović J, Sevigny J, Stanojlović MR, Nedeljković N, Grković I. Erratum to: 17 beta-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes. in Journal of Molecular Neuroscience. 2017;61(3):423-424.
doi:10.1007/s12031-016-0879-4 .

Mitrović, Nataša Lj., Zarić, Marina, Drakulić, Dunja R., Martinović, Jelena, Sevigny, Jean, Stanojlović, Miloš R., Nedeljković, Nadežda, Grković, Ivana, "Erratum to: 17 beta-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes" in Journal of Molecular Neuroscience, 61, no. 3 (2017):423-424,
https://doi.org/10.1007/s12031-016-0879-4 . .

TY  - CONF
AU  - Guševac Stojanović, Ivana
AU  - Drakulić, Dunja R.
AU  - Stanojlović, Miloš R.
AU  - Grković, Ivana
AU  - Martinović, Jelena
AU  - Mitrović, Nataša Lj.
AU  - Zarić, Marina
AU  - Veljković, Filip M.
AU  - Horvat, Anica
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9210
AB  - Reduction  of  oxygen  and  glucose  supply  to  the  brain  due  to  diminished cerebral  blood  flow  leads  to  damage  of  tissue  which  in  experimental conditions  can  be  mimicked  by  permanent  ligation  of  common  carotid arteries  (2VO).  Besides  numerous  genomic  and  non-genomic  processes, cerebral  ischemia  enhances  expression  of  ecto-5'-nucleotidase  (eN),  a  main enzyme  in  the  central  nervous  system  that  produces  potent  neuromodulator and neuroprotector, adenosine. Since progesterone (P), a potent sex steroid, is recognized as neuroprotective, aim of this study was to examine whether repeated  low-dose  P  treatment  is  capable  to  induce  changes  in  activity  and protein expression of eN, at rat cortical membrane fraction following 2VO. Obtained  results  indicate  that  P  modulates  investigated  parameters  and through  stimulation  of  adenosine  generation  might  promote  cytoprotection in ischemic brain.
PB  - Society of Physical Chemists of Serbia
C3  - Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry
T1  - Progesterone upregulates activity and protein expression of efecto-5'-nucleotidase in ischemic brain of male wister rats
SP  - 455
EP  - 458
UR  - https://hdl.handle.net/21.15107/rcub_vinar_9210
ER  - 

@conference{
author = "Guševac Stojanović, Ivana and Drakulić, Dunja R. and Stanojlović, Miloš R. and Grković, Ivana and Martinović, Jelena and Mitrović, Nataša Lj. and Zarić, Marina and Veljković, Filip M. and Horvat, Anica",
year = "2016",
abstract = "Reduction  of  oxygen  and  glucose  supply  to  the  brain  due  to  diminished cerebral  blood  flow  leads  to  damage  of  tissue  which  in  experimental conditions  can  be  mimicked  by  permanent  ligation  of  common  carotid arteries  (2VO).  Besides  numerous  genomic  and  non-genomic  processes, cerebral  ischemia  enhances  expression  of  ecto-5'-nucleotidase  (eN),  a  main enzyme  in  the  central  nervous  system  that  produces  potent  neuromodulator and neuroprotector, adenosine. Since progesterone (P), a potent sex steroid, is recognized as neuroprotective, aim of this study was to examine whether repeated  low-dose  P  treatment  is  capable  to  induce  changes  in  activity  and protein expression of eN, at rat cortical membrane fraction following 2VO. Obtained  results  indicate  that  P  modulates  investigated  parameters  and through  stimulation  of  adenosine  generation  might  promote  cytoprotection in ischemic brain.",
publisher = "Society of Physical Chemists of Serbia",
journal = "Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry",
title = "Progesterone upregulates activity and protein expression of efecto-5'-nucleotidase in ischemic brain of male wister rats",
pages = "455-458",
url = "https://hdl.handle.net/21.15107/rcub_vinar_9210"
}

Guševac Stojanović, I., Drakulić, D. R., Stanojlović, M. R., Grković, I., Martinović, J., Mitrović, N. Lj., Zarić, M., Veljković, F. M.,& Horvat, A.. (2016). Progesterone upregulates activity and protein expression of efecto-5'-nucleotidase in ischemic brain of male wister rats. in Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry
Society of Physical Chemists of Serbia., 455-458.
https://hdl.handle.net/21.15107/rcub_vinar_9210

Guševac Stojanović I, Drakulić DR, Stanojlović MR, Grković I, Martinović J, Mitrović NL, Zarić M, Veljković FM, Horvat A. Progesterone upregulates activity and protein expression of efecto-5'-nucleotidase in ischemic brain of male wister rats. in Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry. 2016;:455-458.
https://hdl.handle.net/21.15107/rcub_vinar_9210 .

Guševac Stojanović, Ivana, Drakulić, Dunja R., Stanojlović, Miloš R., Grković, Ivana, Martinović, Jelena, Mitrović, Nataša Lj., Zarić, Marina, Veljković, Filip M., Horvat, Anica, "Progesterone upregulates activity and protein expression of efecto-5'-nucleotidase in ischemic brain of male wister rats" in Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry (2016):455-458,
https://hdl.handle.net/21.15107/rcub_vinar_9210 .

TY  - JOUR
AU  - Mitrović, Nataša Lj.
AU  - Zarić, Marina
AU  - Drakulić, Dunja R.
AU  - Martinović, Jelena
AU  - Stanojlović, Miloš R.
AU  - Sevigny, Jean
AU  - Horvat, Anica
AU  - Nedeljković, Nadežda
AU  - Grković, Ivana
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1022
AB  - 17 beta-Estradiol (E2) crucially affects several processes in the hippocampus of both sexes. E2 acts upon estradiol receptors ER alpha and ER beta, influencing target gene expression and/or modulates intracellular signaling cascades. Another potent modulator of hippocampal function is nucleoside adenosine, the final product of ectonucleoti-dase cascade, enzymes which hydrolyze extracellular ATP to adenosine. The last and rate-limiting step of the hydrolysis is catalyzed by membrane-bound ecto-50-nucleotidase (eN). Previous findings obtained on adenosine metabolism in brain suggest that eN may be modulated by ovarian steroids. Therefore, the present study reports that the activity and protein abundance of membrane-bound eN fluctuates across the estrus cycle in the hippocampal synaptosomes of female rats. Further, we analyzed the role of E2 and its intracellular receptors on the expression of eN in ovariectomized females. We found that E2 upregulated eN activity and protein abundance in the hippocampal synaptosomes. Application of nonspecific ER antagonist, ICI 182,780 and selective ERa and ERb agonists, PPT and DPN, respectively, demonstrated the involvement of both receptor subtypes in observed actions. Selective ERa receptor agonist, PPT, induced upregulation of both the protein level and activity of eN, while application of selective ERb receptor agonist, DPN, increased only the activity of eN. In both cases, E2 entered into the intracellular compartment and activated ER(s), which was demonstrated by membrane impermeable E2-BSA conjugate. Together these results imply that E2-induced effects on connectivity and functional properties of the hippocampal synapses may be in part mediated through observed effect on eN. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
PB  - Elsevier
T2  - Neuroscience
T1  - 17 beta-ESTRADIOL UPREGULATES ECTO-5 -NUCLEOTIDASE (CD73) IN HIPPOCAMPAL SYNAPTOSOMES OF FEMALE RATS THROUGH ACTION MEDIATED BY ESTROGEN RECEPTOR-alpha AND -beta
VL  - 324
SP  - 286
EP  - 296
DO  - 10.1016/j.neuroscience.2016.03.022
ER  - 

@article{
author = "Mitrović, Nataša Lj. and Zarić, Marina and Drakulić, Dunja R. and Martinović, Jelena and Stanojlović, Miloš R. and Sevigny, Jean and Horvat, Anica and Nedeljković, Nadežda and Grković, Ivana",
year = "2016",
abstract = "17 beta-Estradiol (E2) crucially affects several processes in the hippocampus of both sexes. E2 acts upon estradiol receptors ER alpha and ER beta, influencing target gene expression and/or modulates intracellular signaling cascades. Another potent modulator of hippocampal function is nucleoside adenosine, the final product of ectonucleoti-dase cascade, enzymes which hydrolyze extracellular ATP to adenosine. The last and rate-limiting step of the hydrolysis is catalyzed by membrane-bound ecto-50-nucleotidase (eN). Previous findings obtained on adenosine metabolism in brain suggest that eN may be modulated by ovarian steroids. Therefore, the present study reports that the activity and protein abundance of membrane-bound eN fluctuates across the estrus cycle in the hippocampal synaptosomes of female rats. Further, we analyzed the role of E2 and its intracellular receptors on the expression of eN in ovariectomized females. We found that E2 upregulated eN activity and protein abundance in the hippocampal synaptosomes. Application of nonspecific ER antagonist, ICI 182,780 and selective ERa and ERb agonists, PPT and DPN, respectively, demonstrated the involvement of both receptor subtypes in observed actions. Selective ERa receptor agonist, PPT, induced upregulation of both the protein level and activity of eN, while application of selective ERb receptor agonist, DPN, increased only the activity of eN. In both cases, E2 entered into the intracellular compartment and activated ER(s), which was demonstrated by membrane impermeable E2-BSA conjugate. Together these results imply that E2-induced effects on connectivity and functional properties of the hippocampal synapses may be in part mediated through observed effect on eN. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.",
publisher = "Elsevier",
journal = "Neuroscience",
title = "17 beta-ESTRADIOL UPREGULATES ECTO-5 -NUCLEOTIDASE (CD73) IN HIPPOCAMPAL SYNAPTOSOMES OF FEMALE RATS THROUGH ACTION MEDIATED BY ESTROGEN RECEPTOR-alpha AND -beta",
volume = "324",
pages = "286-296",
doi = "10.1016/j.neuroscience.2016.03.022"
}

Mitrović, N. Lj., Zarić, M., Drakulić, D. R., Martinović, J., Stanojlović, M. R., Sevigny, J., Horvat, A., Nedeljković, N.,& Grković, I.. (2016). 17 beta-ESTRADIOL UPREGULATES ECTO-5 -NUCLEOTIDASE (CD73) IN HIPPOCAMPAL SYNAPTOSOMES OF FEMALE RATS THROUGH ACTION MEDIATED BY ESTROGEN RECEPTOR-alpha AND -beta. in Neuroscience
Elsevier., 324, 286-296.
https://doi.org/10.1016/j.neuroscience.2016.03.022

Mitrović NL, Zarić M, Drakulić DR, Martinović J, Stanojlović MR, Sevigny J, Horvat A, Nedeljković N, Grković I. 17 beta-ESTRADIOL UPREGULATES ECTO-5 -NUCLEOTIDASE (CD73) IN HIPPOCAMPAL SYNAPTOSOMES OF FEMALE RATS THROUGH ACTION MEDIATED BY ESTROGEN RECEPTOR-alpha AND -beta. in Neuroscience. 2016;324:286-296.
doi:10.1016/j.neuroscience.2016.03.022 .

Mitrović, Nataša Lj., Zarić, Marina, Drakulić, Dunja R., Martinović, Jelena, Stanojlović, Miloš R., Sevigny, Jean, Horvat, Anica, Nedeljković, Nadežda, Grković, Ivana, "17 beta-ESTRADIOL UPREGULATES ECTO-5 -NUCLEOTIDASE (CD73) IN HIPPOCAMPAL SYNAPTOSOMES OF FEMALE RATS THROUGH ACTION MEDIATED BY ESTROGEN RECEPTOR-alpha AND -beta" in Neuroscience, 324 (2016):286-296,
https://doi.org/10.1016/j.neuroscience.2016.03.022 . .

TY  - JOUR
AU  - Stanojlović, Miloš R.
AU  - Martinović, Jelena
AU  - Guševac, Ivana
AU  - Grković, Ivana
AU  - Mitrović, Nataša Lj.
AU  - Zarić, Marina
AU  - Horvat, Anica
AU  - Drakulić, Dunja R.
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/527
AB  - Disturbance in blood circulation is associated with numerous pathological conditions characterized by cognitive decline and neurodegeneration. Activation of pro-apoptotic signaling previously detected in the synaptosomal fraction may underlie neurodegeneration in the prefrontal cortex of rats submitted to permanent bilateral common carotid arteries occlusion (two-vessel occlusion, 2VO). 17 beta-Estradiol (E) exerts potent neuroprotective effects in the brain affecting, among other, ischemia-induced pathological changes. As most significant changes in rats submitted to 2VO were observed on 7th day following the insult, of interest was to examine whether 7 day treatment with low dose of E (33.3 mu g/kg/day) prevents formerly reported neurodegeneration and may represent additional therapy during the early post-ischemic period. Role of E treatment on apoptotic pathway was monitored on Bcl-2 family members, cytochrome c, caspase 3 and PARP protein level in the synaptosomal (P2) fraction of the prefrontal cortex. Furthermore, changes of these proteins were examined in the cytosolic, mitochondrial and nuclear fraction, with the emphasis on potential involvement of extracellular signal-regulated kinases (ERK) and protein kinase B (Akt) activation and their role in nuclear translocation of transcriptional nuclear factor kappa B (NF-kB) associated with alteration of Box and Bcl-2 gene expression. The extent of cellular damage was determined using DNA fragmentation and Fluoro-Jade B staining. The absence of activation of apoptotic cascade both in the P2 and cell accompanied with decreased DNA fragmentation and number of degenerating neurons clearly indicates that E treatment ensures the efficient protection against ischemic insult. Moreover, E-mediated modulation of pro-apoptotic signaling in the cortical cellular fractions involves cooperative activation of ERK and Akt, which may be implicated in the observed prevention of neurodegenerative changes. (C) 2015 Elsevier Ltd. All rights reserved.
T2  - Neurochemistry International
T1  - Repeated low-dose 17 beta-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia
VL  - 83-84
SP  - 1
EP  - 8
DO  - 10.1016/j.neuint.2015.03.002
ER  - 

@article{
author = "Stanojlović, Miloš R. and Martinović, Jelena and Guševac, Ivana and Grković, Ivana and Mitrović, Nataša Lj. and Zarić, Marina and Horvat, Anica and Drakulić, Dunja R.",
year = "2015",
abstract = "Disturbance in blood circulation is associated with numerous pathological conditions characterized by cognitive decline and neurodegeneration. Activation of pro-apoptotic signaling previously detected in the synaptosomal fraction may underlie neurodegeneration in the prefrontal cortex of rats submitted to permanent bilateral common carotid arteries occlusion (two-vessel occlusion, 2VO). 17 beta-Estradiol (E) exerts potent neuroprotective effects in the brain affecting, among other, ischemia-induced pathological changes. As most significant changes in rats submitted to 2VO were observed on 7th day following the insult, of interest was to examine whether 7 day treatment with low dose of E (33.3 mu g/kg/day) prevents formerly reported neurodegeneration and may represent additional therapy during the early post-ischemic period. Role of E treatment on apoptotic pathway was monitored on Bcl-2 family members, cytochrome c, caspase 3 and PARP protein level in the synaptosomal (P2) fraction of the prefrontal cortex. Furthermore, changes of these proteins were examined in the cytosolic, mitochondrial and nuclear fraction, with the emphasis on potential involvement of extracellular signal-regulated kinases (ERK) and protein kinase B (Akt) activation and their role in nuclear translocation of transcriptional nuclear factor kappa B (NF-kB) associated with alteration of Box and Bcl-2 gene expression. The extent of cellular damage was determined using DNA fragmentation and Fluoro-Jade B staining. The absence of activation of apoptotic cascade both in the P2 and cell accompanied with decreased DNA fragmentation and number of degenerating neurons clearly indicates that E treatment ensures the efficient protection against ischemic insult. Moreover, E-mediated modulation of pro-apoptotic signaling in the cortical cellular fractions involves cooperative activation of ERK and Akt, which may be implicated in the observed prevention of neurodegenerative changes. (C) 2015 Elsevier Ltd. All rights reserved.",
journal = "Neurochemistry International",
title = "Repeated low-dose 17 beta-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia",
volume = "83-84",
pages = "1-8",
doi = "10.1016/j.neuint.2015.03.002"
}

Stanojlović, M. R., Martinović, J., Guševac, I., Grković, I., Mitrović, N. Lj., Zarić, M., Horvat, A.,& Drakulić, D. R.. (2015). Repeated low-dose 17 beta-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia. in Neurochemistry International, 83-84, 1-8.
https://doi.org/10.1016/j.neuint.2015.03.002

Stanojlović MR, Martinović J, Guševac I, Grković I, Mitrović NL, Zarić M, Horvat A, Drakulić DR. Repeated low-dose 17 beta-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia. in Neurochemistry International. 2015;83-84:1-8.
doi:10.1016/j.neuint.2015.03.002 .

Stanojlović, Miloš R., Martinović, Jelena, Guševac, Ivana, Grković, Ivana, Mitrović, Nataša Lj., Zarić, Marina, Horvat, Anica, Drakulić, Dunja R., "Repeated low-dose 17 beta-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia" in Neurochemistry International, 83-84 (2015):1-8,
https://doi.org/10.1016/j.neuint.2015.03.002 . .