TY  - JOUR
AU  - Guševac Stojanović, Ivana
AU  - Drakulić, Dunja
AU  - Todorović, Ana
AU  - Martinović, Jelena
AU  - Filipović, Nenad
AU  - Stojanović, Zoran
PY  - 2024
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/13127
AB  - While the effects of chronic exposure to microplastic particles (MPs) are extensively studied, the outcomes of a single treatment have received relatively less attention. To investigate MPs’ potential acute toxicity, including their impact on general health status (victual consumption, sensorimotor deficits, and clinical toxicity signs) and serum biochemical parameters (markers of organ/tissue function and oxidative stress indicators), we administered thoroughly characterized MPs (1.4, 35, or 125 mg/kg), generated from polyethylene terephthalate (PET) bottles, to adult male Wistar rats via oral gavage. The MPs’ short-term effects were assessed with well-established tests and methods. The results point to the absence of sensorimotor deficits and clinical toxicity signs, while levels of markers of liver, heart, and kidney function were altered in all MP groups. Decreased victual consumption and increased levels of oxidative stress indicators were evident following treatment with the two higher MP doses. Presented data indicate that examined MPs are able to initiate the development of local changes in tissues and organs within a short time frame, potentially leading to their damage and dysfunction. This study may increase the awareness of the detrimental effects of plastic contamination, as even a single exposure to MPs may provoke adverse health outcomes.
T2  - Toxics
T1  - Acute Toxicity Assessment of Orally Administered Microplastic Particles in Adult Male Wistar Rats
VL  - 12
IS  - 3
SP  - 167
DO  - 10.3390/toxics12030167
ER  - 

@article{
author = "Guševac Stojanović, Ivana and Drakulić, Dunja and Todorović, Ana and Martinović, Jelena and Filipović, Nenad and Stojanović, Zoran",
year = "2024",
abstract = "While the effects of chronic exposure to microplastic particles (MPs) are extensively studied, the outcomes of a single treatment have received relatively less attention. To investigate MPs’ potential acute toxicity, including their impact on general health status (victual consumption, sensorimotor deficits, and clinical toxicity signs) and serum biochemical parameters (markers of organ/tissue function and oxidative stress indicators), we administered thoroughly characterized MPs (1.4, 35, or 125 mg/kg), generated from polyethylene terephthalate (PET) bottles, to adult male Wistar rats via oral gavage. The MPs’ short-term effects were assessed with well-established tests and methods. The results point to the absence of sensorimotor deficits and clinical toxicity signs, while levels of markers of liver, heart, and kidney function were altered in all MP groups. Decreased victual consumption and increased levels of oxidative stress indicators were evident following treatment with the two higher MP doses. Presented data indicate that examined MPs are able to initiate the development of local changes in tissues and organs within a short time frame, potentially leading to their damage and dysfunction. This study may increase the awareness of the detrimental effects of plastic contamination, as even a single exposure to MPs may provoke adverse health outcomes.",
journal = "Toxics",
title = "Acute Toxicity Assessment of Orally Administered Microplastic Particles in Adult Male Wistar Rats",
volume = "12",
number = "3",
pages = "167",
doi = "10.3390/toxics12030167"
}

Guševac Stojanović, I., Drakulić, D., Todorović, A., Martinović, J., Filipović, N.,& Stojanović, Z.. (2024). Acute Toxicity Assessment of Orally Administered Microplastic Particles in Adult Male Wistar Rats. in Toxics, 12(3), 167.
https://doi.org/10.3390/toxics12030167

Guševac Stojanović I, Drakulić D, Todorović A, Martinović J, Filipović N, Stojanović Z. Acute Toxicity Assessment of Orally Administered Microplastic Particles in Adult Male Wistar Rats. in Toxics. 2024;12(3):167.
doi:10.3390/toxics12030167 .

Guševac Stojanović, Ivana, Drakulić, Dunja, Todorović, Ana, Martinović, Jelena, Filipović, Nenad, Stojanović, Zoran, "Acute Toxicity Assessment of Orally Administered Microplastic Particles in Adult Male Wistar Rats" in Toxics, 12, no. 3 (2024):167,
https://doi.org/10.3390/toxics12030167 . .

TY  - CONF
AU  - Bobić, Katarina
AU  - Guševac Stojanović, Ivana
AU  - Todorović, Ana
AU  - Veljković, Filip
AU  - Pejić, Snežana
AU  - Martinović, Jelena
AU  - Drakulić, Dunja
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11060
AB  - Prolonged disturbance of cerebral blood flow causes metabolic insufficiency and neuronal hypofunction, for which there is still no adequate therapeutic strategy. In several animal models of neurodegenerative diseases, progesterone (P4), a potent gonadal steroid hormone, and its metabolites showed neuroprotective outcomes through reduction of oxidative stress and stabilization of membrane lipids and their downstream signalling. As P4 actions in rat striatum following permanent bilateral occlusion of both common carotid arteries are still uncertain, we investigated its capacity to reduce neuronal damage induced by permanent occlusion of both carotid arteries (2VO), focusing on several oxidative stress markers (end products of lipid peroxidation (LPP) and phosphatidylcholine (PC) to lysophosphatidylcholine (LPC) intensity ratio) in crude synaptosomal fraction. Adult male Wistar rats were divided into groups: control ‒ sham operated animals treated with vehicle (commercial flax oil, 1 mg/kg) and permanently occluded animals subjected to either vehicle (commercial flax oil, 1 mg/kg) or P4 (dissolved in commercial flax oil, 1.7 mg/kg). Animals were subcutaneously injected for 7 days and sacrificed 4 h following the last treatment. LPP levels were determined spectrophotometrically, while PC/LPC intensity ratio was estimated by mass spectrometer. Obtained results indicate that P4 treatment alleviates 2VO – induced prooxidative changes by decreasing LPP levels and elevating PC/LPC intensity ratio, and returning them closer to levels observed in controls. According to our findings, P4 treatment in cerebral hypoperfusion model, via targeting striatal cell lipid components and altering lipid profile, might be implicated in reduction of oxidative stress and promotion of protective environment.
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  - Progesterone modulates striatal lipid profile in rat cerebral hypoperfusion model
SP  - 119
EP  - 119
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11060
ER  - 

@conference{
author = "Bobić, Katarina and Guševac Stojanović, Ivana and Todorović, Ana and Veljković, Filip and Pejić, Snežana and Martinović, Jelena and Drakulić, Dunja",
year = "2023",
abstract = "Prolonged disturbance of cerebral blood flow causes metabolic insufficiency and neuronal hypofunction, for which there is still no adequate therapeutic strategy. In several animal models of neurodegenerative diseases, progesterone (P4), a potent gonadal steroid hormone, and its metabolites showed neuroprotective outcomes through reduction of oxidative stress and stabilization of membrane lipids and their downstream signalling. As P4 actions in rat striatum following permanent bilateral occlusion of both common carotid arteries are still uncertain, we investigated its capacity to reduce neuronal damage induced by permanent occlusion of both carotid arteries (2VO), focusing on several oxidative stress markers (end products of lipid peroxidation (LPP) and phosphatidylcholine (PC) to lysophosphatidylcholine (LPC) intensity ratio) in crude synaptosomal fraction. Adult male Wistar rats were divided into groups: control ‒ sham operated animals treated with vehicle (commercial flax oil, 1 mg/kg) and permanently occluded animals subjected to either vehicle (commercial flax oil, 1 mg/kg) or P4 (dissolved in commercial flax oil, 1.7 mg/kg). Animals were subcutaneously injected for 7 days and sacrificed 4 h following the last treatment. LPP levels were determined spectrophotometrically, while PC/LPC intensity ratio was estimated by mass spectrometer. Obtained results indicate that P4 treatment alleviates 2VO – induced prooxidative changes by decreasing LPP levels and elevating PC/LPC intensity ratio, and returning them closer to levels observed in controls. According to our findings, P4 treatment in cerebral hypoperfusion model, via targeting striatal cell lipid components and altering lipid profile, might be implicated in reduction of oxidative stress and promotion of protective environment.",
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 = "Progesterone modulates striatal lipid profile in rat cerebral hypoperfusion model",
pages = "119-119",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11060"
}

Bobić, K., Guševac Stojanović, I., Todorović, A., Veljković, F., Pejić, S., Martinović, J.,& Drakulić, D.. (2023). Progesterone modulates striatal lipid profile 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 Neurocardiological Society., 119-119.
https://hdl.handle.net/21.15107/rcub_vinar_11060

Bobić K, Guševac Stojanović I, Todorović A, Veljković F, Pejić S, Martinović J, Drakulić D. Progesterone modulates striatal lipid profile 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;:119-119.
https://hdl.handle.net/21.15107/rcub_vinar_11060 .

Bobić, Katarina, Guševac Stojanović, Ivana, Todorović, Ana, Veljković, Filip, Pejić, Snežana, Martinović, Jelena, Drakulić, Dunja, "Progesterone modulates striatal lipid profile 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):119-119,
https://hdl.handle.net/21.15107/rcub_vinar_11060 .

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  - 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  - CONF
AU  - Mitrović, Nataša
AU  - Zarić, Marina
AU  - Martinović, Jelena
AU  - Guševac Stojanović, Ivana
AU  - Petrović, Snježana
AU  - Paunović, Marija
AU  - Vučić, Vesna
AU  - Grković, Ivana
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11050
AB  - It is increasingly apparent that the prevention/treatment of neurodegenerative disorders is not only achieved through pharmacological therapy but also through the consumption of natural products. Flaxseed oil (or linseed oil, FSO) derived from the seeds of the flax (Linum usitatissimum L.) gained worldwide awareness as a neuroprotective agent due to its high content of omega-3 polyunsaturated fatty acids (n-3 PUFAs). Thus, the aim of this study was to examine the preventive effects of dietary FSO in trimethyltin (TMT) - induced hippocampal neurodegeneration and gliosis in female Wistar rats. Animals were continuously treated with FSO (1 ml/kg, orally) for two weeks, then received a single dose of TMT (8 mg/kg, i.p.), and application of FSO continued for twenty-one days. Data have convincingly shown that FSO continuous treatment ameliorated TMT-induced neuronal loss in the CA3 hippocampal region and ameliorated astrogliosis and microgliosis. FSO treatment elevated all tested n-3 fatty acids in the hippocampus: α-linolenic acid (ALA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), and consequently increased total amount of n-3 PUFA. However, no changes in n-6 fatty acids due to FSO treatment were observed. Consequently, FSO lowered n-6/n-3 ratio compared to TMT, having a protective effect on fatty acid profile in hippocampus. These findings support beneficial neuroprotective properties of FSO against TMT-induced model of neurodegeneration and hint at a promising preventive use of FSO in hippocampal degeneration and dysfunction
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  - Dietary supplementation with flaxseed oil ameliorates trimethyltin (TMT)-induced neurodegeneration and gliosis in female Wistar rats
SP  - 81
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11050
ER  - 

@conference{
author = "Mitrović, Nataša and Zarić, Marina and Martinović, Jelena and Guševac Stojanović, Ivana and Petrović, Snježana and Paunović, Marija and Vučić, Vesna and Grković, Ivana",
year = "2023",
abstract = "It is increasingly apparent that the prevention/treatment of neurodegenerative disorders is not only achieved through pharmacological therapy but also through the consumption of natural products. Flaxseed oil (or linseed oil, FSO) derived from the seeds of the flax (Linum usitatissimum L.) gained worldwide awareness as a neuroprotective agent due to its high content of omega-3 polyunsaturated fatty acids (n-3 PUFAs). Thus, the aim of this study was to examine the preventive effects of dietary FSO in trimethyltin (TMT) - induced hippocampal neurodegeneration and gliosis in female Wistar rats. Animals were continuously treated with FSO (1 ml/kg, orally) for two weeks, then received a single dose of TMT (8 mg/kg, i.p.), and application of FSO continued for twenty-one days. Data have convincingly shown that FSO continuous treatment ameliorated TMT-induced neuronal loss in the CA3 hippocampal region and ameliorated astrogliosis and microgliosis. FSO treatment elevated all tested n-3 fatty acids in the hippocampus: α-linolenic acid (ALA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), and consequently increased total amount of n-3 PUFA. However, no changes in n-6 fatty acids due to FSO treatment were observed. Consequently, FSO lowered n-6/n-3 ratio compared to TMT, having a protective effect on fatty acid profile in hippocampus. These findings support beneficial neuroprotective properties of FSO against TMT-induced model of neurodegeneration and hint at a promising preventive use of FSO in hippocampal degeneration and dysfunction",
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 = "Dietary supplementation with flaxseed oil ameliorates trimethyltin (TMT)-induced neurodegeneration and gliosis in female Wistar rats",
pages = "81",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11050"
}

Mitrović, N., Zarić, M., Martinović, J., Guševac Stojanović, I., Petrović, S., Paunović, M., Vučić, V.,& Grković, I.. (2023). Dietary supplementation with flaxseed oil ameliorates trimethyltin (TMT)-induced neurodegeneration and gliosis in female 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., 81.
https://hdl.handle.net/21.15107/rcub_vinar_11050

Mitrović N, Zarić M, Martinović J, Guševac Stojanović I, Petrović S, Paunović M, Vučić V, Grković I. Dietary supplementation with flaxseed oil ameliorates trimethyltin (TMT)-induced neurodegeneration and gliosis in female Wistar rats. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade. 2023;:81.
https://hdl.handle.net/21.15107/rcub_vinar_11050 .

Mitrović, Nataša, Zarić, Marina, Martinović, Jelena, Guševac Stojanović, Ivana, Petrović, Snježana, Paunović, Marija, Vučić, Vesna, Grković, Ivana, "Dietary supplementation with flaxseed oil ameliorates trimethyltin (TMT)-induced neurodegeneration and gliosis in female Wistar rats" in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade (2023):81,
https://hdl.handle.net/21.15107/rcub_vinar_11050 .

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  - CONF
AU  - Bobić, Katarina
AU  - Guševac Stojanović, Ivana
AU  - Todorović, Ana
AU  - Veljković, Filip
AU  - Pejić, Snežana
AU  - Martinović, Jelena
AU  - Drakulić, Dunja
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11007
AB  - Progesterone (P4), a naturally occurring gonadal hormone in the brain, and its metabolites, are proposed as potential therapeutic agents in various neurodegenerative animal models given that their neuroprotective properties might be associated with amelioration of oxidative stress. Since P4 actions in rat striatum upon permanent ligation of both common carotid arteries are still ambiguous, the present study aimed to evaluate whether 7 days lasting P4 treatment could modulate the levels of several striatal oxidative stress indicators, including prooxidant/antioxidant balance (PAB), advanced oxidation protein products (AOPP) and products of lipid peroxidation (LPO). For the purpose of the experiment, adult male Wistar rats (n = 12) were divided into 3 groups: sham-operated animals subjected to vehicle (commercial flax oil, 1 mg/kg, s.c., Sham + V), occluded animals treated either with vehicle (2VO + V) or P4 (dissolved in commercial flax oil, 1.7 mg/kg, s.c., 2VO + P4). Rats were sacrificed 4 h following the last treatment1 and striatal synaptosomal fraction was used for further biochemical analyses 2. Our results demonstrate that investigated oxidative stress indicators are affected to the different extents by P4 treatment. Namely, in comparison to the Sham + V group, PAB level was elevated in 2VO + V rats, while in 2VO + P4 animals it was downregulated to the levels observed in the Sham + V group. In parallel, 2VO-induced alteration of AOPP was decreased following P4 treatment whereas LPO level was still slightly elevated. Overall, our findings suggest that P4 might manifest antioxidative features in the striatum of hypoperfused rats.
PB  - Belgrade : Faculty of Chemistry : Serbian Biochemical Society
C3  - Serbian Biochemical Society : 11th conference - "Amazing Biochemistry" : proceedings ; September 22-23, 2022; Novi Sad, Serbia
T1  - Antioxidative properties of progesterone in striatum of permanently occluded adult male Wistar rats
SP  - 53
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11007
ER  - 

@conference{
author = "Bobić, Katarina and Guševac Stojanović, Ivana and Todorović, Ana and Veljković, Filip and Pejić, Snežana and Martinović, Jelena and Drakulić, Dunja",
year = "2022",
abstract = "Progesterone (P4), a naturally occurring gonadal hormone in the brain, and its metabolites, are proposed as potential therapeutic agents in various neurodegenerative animal models given that their neuroprotective properties might be associated with amelioration of oxidative stress. Since P4 actions in rat striatum upon permanent ligation of both common carotid arteries are still ambiguous, the present study aimed to evaluate whether 7 days lasting P4 treatment could modulate the levels of several striatal oxidative stress indicators, including prooxidant/antioxidant balance (PAB), advanced oxidation protein products (AOPP) and products of lipid peroxidation (LPO). For the purpose of the experiment, adult male Wistar rats (n = 12) were divided into 3 groups: sham-operated animals subjected to vehicle (commercial flax oil, 1 mg/kg, s.c., Sham + V), occluded animals treated either with vehicle (2VO + V) or P4 (dissolved in commercial flax oil, 1.7 mg/kg, s.c., 2VO + P4). Rats were sacrificed 4 h following the last treatment1 and striatal synaptosomal fraction was used for further biochemical analyses 2. Our results demonstrate that investigated oxidative stress indicators are affected to the different extents by P4 treatment. Namely, in comparison to the Sham + V group, PAB level was elevated in 2VO + V rats, while in 2VO + P4 animals it was downregulated to the levels observed in the Sham + V group. In parallel, 2VO-induced alteration of AOPP was decreased following P4 treatment whereas LPO level was still slightly elevated. Overall, our findings suggest that P4 might manifest antioxidative features in the striatum of hypoperfused rats.",
publisher = "Belgrade : Faculty of Chemistry : Serbian Biochemical Society",
journal = "Serbian Biochemical Society : 11th conference - "Amazing Biochemistry" : proceedings ; September 22-23, 2022; Novi Sad, Serbia",
title = "Antioxidative properties of progesterone in striatum of permanently occluded adult male Wistar rats",
pages = "53",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11007"
}

Bobić, K., Guševac Stojanović, I., Todorović, A., Veljković, F., Pejić, S., Martinović, J.,& Drakulić, D.. (2022). Antioxidative properties of progesterone in striatum of permanently occluded adult male Wistar rats. in Serbian Biochemical Society : 11th conference - "Amazing Biochemistry" : proceedings ; September 22-23, 2022; Novi Sad, Serbia
Belgrade : Faculty of Chemistry : Serbian Biochemical Society., 53.
https://hdl.handle.net/21.15107/rcub_vinar_11007

Bobić K, Guševac Stojanović I, Todorović A, Veljković F, Pejić S, Martinović J, Drakulić D. Antioxidative properties of progesterone in striatum of permanently occluded adult male Wistar rats. in Serbian Biochemical Society : 11th conference - "Amazing Biochemistry" : proceedings ; September 22-23, 2022; Novi Sad, Serbia. 2022;:53.
https://hdl.handle.net/21.15107/rcub_vinar_11007 .

Bobić, Katarina, Guševac Stojanović, Ivana, Todorović, Ana, Veljković, Filip, Pejić, Snežana, Martinović, Jelena, Drakulić, Dunja, "Antioxidative properties of progesterone in striatum of permanently occluded adult male Wistar rats" in Serbian Biochemical Society : 11th conference - "Amazing Biochemistry" : proceedings ; September 22-23, 2022; Novi Sad, Serbia (2022):53,
https://hdl.handle.net/21.15107/rcub_vinar_11007 .

TY  - CONF
AU  - Martinović, Jelena
AU  - Guševac Stojanović, Ivana
AU  - Zarić, M.
AU  - Todorović, Ana
AU  - Veljković, Filip
AU  - Pejić, Snežana
AU  - Stojanović, Zoran
AU  - Mitrović, N.
AU  - Grković, Ivana
AU  - Drakulić, Dunja
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11399
AB  - D-galactose (d-gal) is an important physiological nutrient. According to thewidely accepted aging metabolic theory d-gal at high levels can be convertedinto aldose and hydroperoxide, resulting in the overproduction of reactiveoxygen species (ROS). Increased ROS levels may subsequently cause oxidative stress, inflammation, mitochondrial dysfunction, and apoptosis which are hallmarks of natural senescence as well as various pathological conditions. We investigated the effects of chronic oral d-gal intake (200 mg/kg and 500 mg/kg for 6 weeks) on physiological, neurological and toxicity parameters in 3 months old male Wistar rats. The obtained results indicate that body weight, food intake, serum glucose, neurological and toxicity status remained unaffected while urine proteins were significantly increased in d-gal treated rats. Although there was no effect on the general health status of the animals, our findings suggest that chronic oral d-gal administration may lead to renal dysfunction.
PB  - Belgrade : Vinča Institute of Nuclear Sciences
C3  - 7th Workshop Specific Methods for Food Safety and Quality, September 22nd, 2021, Belgrade, Serbia, 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry - Physical Chemistry
T1  - Effects of chronic oral D-galactose treatment on general health status in male Wistar rats
SP  - 115
EP  - 118
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11399
ER  - 

@conference{
author = "Martinović, Jelena and Guševac Stojanović, Ivana and Zarić, M. and Todorović, Ana and Veljković, Filip and Pejić, Snežana and Stojanović, Zoran and Mitrović, N. and Grković, Ivana and Drakulić, Dunja",
year = "2021",
abstract = "D-galactose (d-gal) is an important physiological nutrient. According to thewidely accepted aging metabolic theory d-gal at high levels can be convertedinto aldose and hydroperoxide, resulting in the overproduction of reactiveoxygen species (ROS). Increased ROS levels may subsequently cause oxidative stress, inflammation, mitochondrial dysfunction, and apoptosis which are hallmarks of natural senescence as well as various pathological conditions. We investigated the effects of chronic oral d-gal intake (200 mg/kg and 500 mg/kg for 6 weeks) on physiological, neurological and toxicity parameters in 3 months old male Wistar rats. The obtained results indicate that body weight, food intake, serum glucose, neurological and toxicity status remained unaffected while urine proteins were significantly increased in d-gal treated rats. Although there was no effect on the general health status of the animals, our findings suggest that chronic oral d-gal administration may lead to renal dysfunction.",
publisher = "Belgrade : Vinča Institute of Nuclear Sciences",
journal = "7th Workshop Specific Methods for Food Safety and Quality, September 22nd, 2021, Belgrade, Serbia, 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry - Physical Chemistry",
title = "Effects of chronic oral D-galactose treatment on general health status in male Wistar rats",
pages = "115-118",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11399"
}

Martinović, J., Guševac Stojanović, I., Zarić, M., Todorović, A., Veljković, F., Pejić, S., Stojanović, Z., Mitrović, N., Grković, I.,& Drakulić, D.. (2021). Effects of chronic oral D-galactose treatment on general health status in male Wistar rats. in 7th Workshop Specific Methods for Food Safety and Quality, September 22nd, 2021, Belgrade, Serbia, 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry - Physical Chemistry
Belgrade : Vinča Institute of Nuclear Sciences., 115-118.
https://hdl.handle.net/21.15107/rcub_vinar_11399

Martinović J, Guševac Stojanović I, Zarić M, Todorović A, Veljković F, Pejić S, Stojanović Z, Mitrović N, Grković I, Drakulić D. Effects of chronic oral D-galactose treatment on general health status in male Wistar rats. in 7th Workshop Specific Methods for Food Safety and Quality, September 22nd, 2021, Belgrade, Serbia, 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry - Physical Chemistry. 2021;:115-118.
https://hdl.handle.net/21.15107/rcub_vinar_11399 .

Martinović, Jelena, Guševac Stojanović, Ivana, Zarić, M., Todorović, Ana, Veljković, Filip, Pejić, Snežana, Stojanović, Zoran, Mitrović, N., Grković, Ivana, Drakulić, Dunja, "Effects of chronic oral D-galactose treatment on general health status in male Wistar rats" in 7th Workshop Specific Methods for Food Safety and Quality, September 22nd, 2021, Belgrade, Serbia, 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry - Physical Chemistry (2021):115-118,
https://hdl.handle.net/21.15107/rcub_vinar_11399 .

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  - 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  - 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  - 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  - Stanojlović, Miloš R.
AU  - Guševac, Ivana
AU  - Grković, Ivana
AU  - Mitrović, Nataša Lj.
AU  - Martinović, Jelena
AU  - Horvat, Anica
AU  - Drakulić, Dunja R.
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1156
AB  - Although a substantial number of pre-clinical and experimental studies have investigated effects of 17 beta-estradiol, its precise molecular mechanism of action in the early state of chronic cerebral hypoperfusion remains controversial. The present study attempted to verify whether post-ischemic estradiol treatment (33.3 mu g/kg for seven consecutive days) affects previously reported number of hippocampal apoptotic cells and amount of DNA fragmentation characteristic for apoptosis as well as the expression of key elements within synaptosomal Akt and Erk signal transduction pathways (NF-kappa B, Bax, Bcl-2, cytochrome C, caspase 3, and PARP). Additionally, alterations of aforementioned molecules linked to protection in various neurodegenerative disorders were monitored in the cytosolic, mitochondrial, and nuclear fractions associating investigated kinases and NF-kappa B with gene expression of their downstream effectors-Bcl-2, Bax, and caspase 3. The results revealed that an initial increase in the number of apoptotic cells and amount of DNA fragmentation induced by chronic cerebral hypoperfusion was significantly reduced by 17 beta-estradiol. In synaptic regions, an altered profile with respect to the protein expression of Bcl-2 and phosphorylated Akt was detected, although the level of other examined proteins was not modified. In other investigated sub-cellular fractions, 17 beta-estradiol elicited phosphorylation and translocation of Akt and Erk along with modulation of the expression of their subsequent effectors. Our findings support the concept that repeated post-ischemic 17 beta-estradiol treatment attenuates neurodegeneration induced by chronic cerebral hypoperfusion in hippocampus through the activation of investigated kinases and regulation of their downstream molecules in sub-cellular manner indicating a time window and regime of its administration as a valid therapeutic intervention.
T2  - Cellular and Molecular Neurobiology
T1  - Repeated Estradiol Treatment Attenuates Chronic Cerebral Hypoperfusion-Induced Neurodegeneration in Rat Hippocampus
VL  - 36
IS  - 6
SP  - 989
EP  - 999
DO  - 10.1007/s10571-015-0289-0
ER  - 

@article{
author = "Stanojlović, Miloš R. and Guševac, Ivana and Grković, Ivana and Mitrović, Nataša Lj. and Martinović, Jelena and Horvat, Anica and Drakulić, Dunja R.",
year = "2016",
abstract = "Although a substantial number of pre-clinical and experimental studies have investigated effects of 17 beta-estradiol, its precise molecular mechanism of action in the early state of chronic cerebral hypoperfusion remains controversial. The present study attempted to verify whether post-ischemic estradiol treatment (33.3 mu g/kg for seven consecutive days) affects previously reported number of hippocampal apoptotic cells and amount of DNA fragmentation characteristic for apoptosis as well as the expression of key elements within synaptosomal Akt and Erk signal transduction pathways (NF-kappa B, Bax, Bcl-2, cytochrome C, caspase 3, and PARP). Additionally, alterations of aforementioned molecules linked to protection in various neurodegenerative disorders were monitored in the cytosolic, mitochondrial, and nuclear fractions associating investigated kinases and NF-kappa B with gene expression of their downstream effectors-Bcl-2, Bax, and caspase 3. The results revealed that an initial increase in the number of apoptotic cells and amount of DNA fragmentation induced by chronic cerebral hypoperfusion was significantly reduced by 17 beta-estradiol. In synaptic regions, an altered profile with respect to the protein expression of Bcl-2 and phosphorylated Akt was detected, although the level of other examined proteins was not modified. In other investigated sub-cellular fractions, 17 beta-estradiol elicited phosphorylation and translocation of Akt and Erk along with modulation of the expression of their subsequent effectors. Our findings support the concept that repeated post-ischemic 17 beta-estradiol treatment attenuates neurodegeneration induced by chronic cerebral hypoperfusion in hippocampus through the activation of investigated kinases and regulation of their downstream molecules in sub-cellular manner indicating a time window and regime of its administration as a valid therapeutic intervention.",
journal = "Cellular and Molecular Neurobiology",
title = "Repeated Estradiol Treatment Attenuates Chronic Cerebral Hypoperfusion-Induced Neurodegeneration in Rat Hippocampus",
volume = "36",
number = "6",
pages = "989-999",
doi = "10.1007/s10571-015-0289-0"
}

Stanojlović, M. R., Guševac, I., Grković, I., Mitrović, N. Lj., Martinović, J., Horvat, A.,& Drakulić, D. R.. (2016). Repeated Estradiol Treatment Attenuates Chronic Cerebral Hypoperfusion-Induced Neurodegeneration in Rat Hippocampus. in Cellular and Molecular Neurobiology, 36(6), 989-999.
https://doi.org/10.1007/s10571-015-0289-0

Stanojlović MR, Guševac I, Grković I, Mitrović NL, Martinović J, Horvat A, Drakulić DR. Repeated Estradiol Treatment Attenuates Chronic Cerebral Hypoperfusion-Induced Neurodegeneration in Rat Hippocampus. in Cellular and Molecular Neurobiology. 2016;36(6):989-999.
doi:10.1007/s10571-015-0289-0 .

Stanojlović, Miloš R., Guševac, Ivana, Grković, Ivana, Mitrović, Nataša Lj., Martinović, Jelena, Horvat, Anica, Drakulić, Dunja R., "Repeated Estradiol Treatment Attenuates Chronic Cerebral Hypoperfusion-Induced Neurodegeneration in Rat Hippocampus" in Cellular and Molecular Neurobiology, 36, no. 6 (2016):989-999,
https://doi.org/10.1007/s10571-015-0289-0 . .

TY  - JOUR
AU  - Mitrović, Nataša Lj.
AU  - Guševac, Ivana
AU  - Drakulić, Dunja R.
AU  - Stanojlović, Miloš R.
AU  - Martinović, Jelena
AU  - Sevigny, Jean
AU  - Horvat, Anica
AU  - Nedeljković, Nadežda
AU  - Grković, Ivana
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1222
AB  - Ecto-5-nucleotidase (eN), a membrane rate-limiting enzyme of the purine catabolic pathway, catalyzes the conversion of AMP to adenosine involved in the regulation of many brain physiological and pathological processes. Since gender fundamentally determines hormonal milieu in the body and brain, it is reasonable to assume that sex differences in the activity of various signaling systems, including adenosine, may be generated by gonadal steroids. Thus, we examined expression of eN as a component of adenosine signaling system in the basal state in cerebral cortex and hippocampus of male and female rats at gene, protein and functional level, as well as in the state of gonadal hormone deprivation, induced by ovariectomy (OVX), whereas impact of steroid hormones was explored after repeated administration of 17 alpha-estradiol, 17 beta-estradiol and progesterone for seven consecutive days. Results showed regional and sex-related differences in basal eN activity level, with the highest AMP hydrolysis observed in the hippocampus of male rats. Furthermore, ovarian steroids do not contribute to basal gene eN expression or the activity in cortical and hippocampal region of female rats. However, protein eN expression was increased in OVX rats in both investigated region. Investigated exogenous steroids had no influence on eN expression in male brain, while in OVX females alterations in eN activity were induced. The observed effects in female rats were different between examined regions e.g. in cortex, applied treatments predominantly decreased whereas in hippocampus increased eN activity. Based on the presented results, eN exerts regional and sex-related response in basal state as well as after treatment with female gonadal hormones, however the exact mechanisms of sex steroids actions on eN remain unclear and should be fully explored. (C) 2016 Elsevier Inc. All rights reserved.
T2  - General and Comparative Endocrinology
T1  - Regional and sex-related differences in modulating effects of female sex steroids on ecto-5-nucleotidase expression in the rat cerebral cortex and hippocampus
VL  - 235
SP  - 100
EP  - 107
DO  - 10.1016/j.ygcen.2016.06.018
ER  - 

@article{
author = "Mitrović, Nataša Lj. and Guševac, Ivana and Drakulić, Dunja R. and Stanojlović, Miloš R. and Martinović, Jelena and Sevigny, Jean and Horvat, Anica and Nedeljković, Nadežda and Grković, Ivana",
year = "2016",
abstract = "Ecto-5-nucleotidase (eN), a membrane rate-limiting enzyme of the purine catabolic pathway, catalyzes the conversion of AMP to adenosine involved in the regulation of many brain physiological and pathological processes. Since gender fundamentally determines hormonal milieu in the body and brain, it is reasonable to assume that sex differences in the activity of various signaling systems, including adenosine, may be generated by gonadal steroids. Thus, we examined expression of eN as a component of adenosine signaling system in the basal state in cerebral cortex and hippocampus of male and female rats at gene, protein and functional level, as well as in the state of gonadal hormone deprivation, induced by ovariectomy (OVX), whereas impact of steroid hormones was explored after repeated administration of 17 alpha-estradiol, 17 beta-estradiol and progesterone for seven consecutive days. Results showed regional and sex-related differences in basal eN activity level, with the highest AMP hydrolysis observed in the hippocampus of male rats. Furthermore, ovarian steroids do not contribute to basal gene eN expression or the activity in cortical and hippocampal region of female rats. However, protein eN expression was increased in OVX rats in both investigated region. Investigated exogenous steroids had no influence on eN expression in male brain, while in OVX females alterations in eN activity were induced. The observed effects in female rats were different between examined regions e.g. in cortex, applied treatments predominantly decreased whereas in hippocampus increased eN activity. Based on the presented results, eN exerts regional and sex-related response in basal state as well as after treatment with female gonadal hormones, however the exact mechanisms of sex steroids actions on eN remain unclear and should be fully explored. (C) 2016 Elsevier Inc. All rights reserved.",
journal = "General and Comparative Endocrinology",
title = "Regional and sex-related differences in modulating effects of female sex steroids on ecto-5-nucleotidase expression in the rat cerebral cortex and hippocampus",
volume = "235",
pages = "100-107",
doi = "10.1016/j.ygcen.2016.06.018"
}

Mitrović, N. Lj., Guševac, I., Drakulić, D. R., Stanojlović, M. R., Martinović, J., Sevigny, J., Horvat, A., Nedeljković, N.,& Grković, I.. (2016). Regional and sex-related differences in modulating effects of female sex steroids on ecto-5-nucleotidase expression in the rat cerebral cortex and hippocampus. in General and Comparative Endocrinology, 235, 100-107.
https://doi.org/10.1016/j.ygcen.2016.06.018

Mitrović NL, Guševac I, Drakulić DR, Stanojlović MR, Martinović J, Sevigny J, Horvat A, Nedeljković N, Grković I. Regional and sex-related differences in modulating effects of female sex steroids on ecto-5-nucleotidase expression in the rat cerebral cortex and hippocampus. in General and Comparative Endocrinology. 2016;235:100-107.
doi:10.1016/j.ygcen.2016.06.018 .

Mitrović, Nataša Lj., Guševac, Ivana, Drakulić, Dunja R., Stanojlović, Miloš R., Martinović, Jelena, Sevigny, Jean, Horvat, Anica, Nedeljković, Nadežda, Grković, Ivana, "Regional and sex-related differences in modulating effects of female sex steroids on ecto-5-nucleotidase expression in the rat cerebral cortex and hippocampus" in General and Comparative Endocrinology, 235 (2016):100-107,
https://doi.org/10.1016/j.ygcen.2016.06.018 . .

TY  - JOUR
AU  - Drakulić, Dunja R.
AU  - Stanojlović, Miloš R.
AU  - Nedeljković, Nadežda
AU  - Grković, Ivana
AU  - Velickovic, Natasa
AU  - Guševac, Ivana
AU  - Mitrović, Nataša Lj.
AU  - Buzadzic, Ivana
AU  - Horvat, Anica
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/446
AB  - Although dexamethasone (DEX), a synthetic glucocorticoid receptor (GR) analog with profound effects on energy metabolism, immune system, and hypothalamic-pituitary-adrenal axis, is widely used therapeutically, its impact on the brain is poorly understood. The aim of the present study was to explore the effect of repeated low-dose DEX administration on the activity and expression of the ectonucleotidase enzymes which hydrolyze and therefore control extracellular ATP and adenosine concentrations in the synaptic cleft. Ectonucleotidases tested were ectonucleoside triphosphate diphosphohydrolase 1-3 (NTPDase1-3) and ecto-5-nucleotidase (eN), whereas the effects were evaluated in two brain areas that show different sensitivity to glucocorticoid action, hippocampus, and cerebral cortex. In the hippocampus, but not in cerebral cortex, modest level of neurodegenerative changes as well as increase in ATP, ADP, and AMP hydrolysis and upregulation of NTPDase1 and eN mRNA expression ensued under the influence of DEX. The observed pattern of ectonucleotidase activation, which creates tissue volume with enhanced capacity for adenosine formation, is the hallmark of the response after different insults to the brain.
T2  - Journal of Molecular Neuroscience
T1  - Upregulation of Nucleoside Triphosphate Diphosphohydrolase-1 and Ecto-5-Nucleotidase in Rat Hippocampus after Repeated Low-Dose Dexamethasone Administration
VL  - 55
IS  - 4
SP  - 959
EP  - 967
DO  - 10.1007/s12031-014-0452-y
ER  - 

@article{
author = "Drakulić, Dunja R. and Stanojlović, Miloš R. and Nedeljković, Nadežda and Grković, Ivana and Velickovic, Natasa and Guševac, Ivana and Mitrović, Nataša Lj. and Buzadzic, Ivana and Horvat, Anica",
year = "2015",
abstract = "Although dexamethasone (DEX), a synthetic glucocorticoid receptor (GR) analog with profound effects on energy metabolism, immune system, and hypothalamic-pituitary-adrenal axis, is widely used therapeutically, its impact on the brain is poorly understood. The aim of the present study was to explore the effect of repeated low-dose DEX administration on the activity and expression of the ectonucleotidase enzymes which hydrolyze and therefore control extracellular ATP and adenosine concentrations in the synaptic cleft. Ectonucleotidases tested were ectonucleoside triphosphate diphosphohydrolase 1-3 (NTPDase1-3) and ecto-5-nucleotidase (eN), whereas the effects were evaluated in two brain areas that show different sensitivity to glucocorticoid action, hippocampus, and cerebral cortex. In the hippocampus, but not in cerebral cortex, modest level of neurodegenerative changes as well as increase in ATP, ADP, and AMP hydrolysis and upregulation of NTPDase1 and eN mRNA expression ensued under the influence of DEX. The observed pattern of ectonucleotidase activation, which creates tissue volume with enhanced capacity for adenosine formation, is the hallmark of the response after different insults to the brain.",
journal = "Journal of Molecular Neuroscience",
title = "Upregulation of Nucleoside Triphosphate Diphosphohydrolase-1 and Ecto-5-Nucleotidase in Rat Hippocampus after Repeated Low-Dose Dexamethasone Administration",
volume = "55",
number = "4",
pages = "959-967",
doi = "10.1007/s12031-014-0452-y"
}

Drakulić, D. R., Stanojlović, M. R., Nedeljković, N., Grković, I., Velickovic, N., Guševac, I., Mitrović, N. Lj., Buzadzic, I.,& Horvat, A.. (2015). Upregulation of Nucleoside Triphosphate Diphosphohydrolase-1 and Ecto-5-Nucleotidase in Rat Hippocampus after Repeated Low-Dose Dexamethasone Administration. in Journal of Molecular Neuroscience, 55(4), 959-967.
https://doi.org/10.1007/s12031-014-0452-y

Drakulić DR, Stanojlović MR, Nedeljković N, Grković I, Velickovic N, Guševac I, Mitrović NL, Buzadzic I, Horvat A. Upregulation of Nucleoside Triphosphate Diphosphohydrolase-1 and Ecto-5-Nucleotidase in Rat Hippocampus after Repeated Low-Dose Dexamethasone Administration. in Journal of Molecular Neuroscience. 2015;55(4):959-967.
doi:10.1007/s12031-014-0452-y .

Drakulić, Dunja R., Stanojlović, Miloš R., Nedeljković, Nadežda, Grković, Ivana, Velickovic, Natasa, Guševac, Ivana, Mitrović, Nataša Lj., Buzadzic, Ivana, Horvat, Anica, "Upregulation of Nucleoside Triphosphate Diphosphohydrolase-1 and Ecto-5-Nucleotidase in Rat Hippocampus after Repeated Low-Dose Dexamethasone Administration" in Journal of Molecular Neuroscience, 55, no. 4 (2015):959-967,
https://doi.org/10.1007/s12031-014-0452-y . .

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 . .

TY  - JOUR
AU  - Stanojlović, Miloš R.
AU  - Guševac, Ivana
AU  - Grković, Ivana
AU  - Martinović, Jelena
AU  - Mitrović, Nataša Lj.
AU  - Zarić, Marina
AU  - Horvat, Anica
AU  - Drakulić, Dunja R.
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/846
AB  - The present study attempted to investigate how chronic cerebral hypoperfusion (CCH) and repeated low-dose progesterone (P) treatment affect gene and protein expression, subcellular distribution of key apoptotic elements within protein kinase B (Akt) and extracellular signal-regulated kinases (Erk) signal transduction pathways, as well as neurodegenerative processes and behavior. The results revealed the absence of Erk activation in CCH in cytosolic and synaptosomal fractions, indicating a lower threshold of Akt activation in brain ischemia, while P increased their levels above control values. CCH induced an increase in caspase 3 (Casp 3) and poly (ADP-ribose) polymerase (PARP) gene and protein expression. However, P restored expression of examined molecules in all observed fractions, except for the levels of Casp 3 in synapses which highlighted its possible non-apoptotic or even protective function. Our study showed the absence of nuclear factor kappa-light-chain-enhancer of activated b cells (NF-kappa B) response to this type of ischemic condition and its strong activation under the influence of P. Further, the initial increase in the number of apoptotic cells and amount of DNA fragmentation induced by CCH was significantly reduced by P. Finally, P reversed the CCH-induced reduction in locomotor activity, while promoting a substantial decrease in anxiety-related behavior. Our findings support the concept that repeated low-dose post-ischemic P treatment reduces CCH-induced neurodegeneration in the hippocampus. Neuroprotection is initiated through the activation of investigated kinases and regulation of their downstream molecules in subcellular specific manner, indicating that this treatment may be a promising therapy for alleviation of CCH-induced pathologies. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
PB  - Elsevier
T2  - Neuroscience
T1  - Effects of Chronic Cerebral Hypoperfusion and Low-Dose Progesterone Treatment on Apoptotic Processes, Expression and Subcellular Localization of Key Elements Within Akt and Erk Signaling Pathways in Rat Hippocampus
VL  - 311
SP  - 308
EP  - 321
DO  - 10.1016/j.neuroscience.2015.10.040
ER  - 

@article{
author = "Stanojlović, Miloš R. and Guševac, Ivana and Grković, Ivana and Martinović, Jelena and Mitrović, Nataša Lj. and Zarić, Marina and Horvat, Anica and Drakulić, Dunja R.",
year = "2015",
abstract = "The present study attempted to investigate how chronic cerebral hypoperfusion (CCH) and repeated low-dose progesterone (P) treatment affect gene and protein expression, subcellular distribution of key apoptotic elements within protein kinase B (Akt) and extracellular signal-regulated kinases (Erk) signal transduction pathways, as well as neurodegenerative processes and behavior. The results revealed the absence of Erk activation in CCH in cytosolic and synaptosomal fractions, indicating a lower threshold of Akt activation in brain ischemia, while P increased their levels above control values. CCH induced an increase in caspase 3 (Casp 3) and poly (ADP-ribose) polymerase (PARP) gene and protein expression. However, P restored expression of examined molecules in all observed fractions, except for the levels of Casp 3 in synapses which highlighted its possible non-apoptotic or even protective function. Our study showed the absence of nuclear factor kappa-light-chain-enhancer of activated b cells (NF-kappa B) response to this type of ischemic condition and its strong activation under the influence of P. Further, the initial increase in the number of apoptotic cells and amount of DNA fragmentation induced by CCH was significantly reduced by P. Finally, P reversed the CCH-induced reduction in locomotor activity, while promoting a substantial decrease in anxiety-related behavior. Our findings support the concept that repeated low-dose post-ischemic P treatment reduces CCH-induced neurodegeneration in the hippocampus. Neuroprotection is initiated through the activation of investigated kinases and regulation of their downstream molecules in subcellular specific manner, indicating that this treatment may be a promising therapy for alleviation of CCH-induced pathologies. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.",
publisher = "Elsevier",
journal = "Neuroscience",
title = "Effects of Chronic Cerebral Hypoperfusion and Low-Dose Progesterone Treatment on Apoptotic Processes, Expression and Subcellular Localization of Key Elements Within Akt and Erk Signaling Pathways in Rat Hippocampus",
volume = "311",
pages = "308-321",
doi = "10.1016/j.neuroscience.2015.10.040"
}

Stanojlović, M. R., Guševac, I., Grković, I., Martinović, J., Mitrović, N. Lj., Zarić, M., Horvat, A.,& Drakulić, D. R.. (2015). Effects of Chronic Cerebral Hypoperfusion and Low-Dose Progesterone Treatment on Apoptotic Processes, Expression and Subcellular Localization of Key Elements Within Akt and Erk Signaling Pathways in Rat Hippocampus. in Neuroscience
Elsevier., 311, 308-321.
https://doi.org/10.1016/j.neuroscience.2015.10.040

Stanojlović MR, Guševac I, Grković I, Martinović J, Mitrović NL, Zarić M, Horvat A, Drakulić DR. Effects of Chronic Cerebral Hypoperfusion and Low-Dose Progesterone Treatment on Apoptotic Processes, Expression and Subcellular Localization of Key Elements Within Akt and Erk Signaling Pathways in Rat Hippocampus. in Neuroscience. 2015;311:308-321.
doi:10.1016/j.neuroscience.2015.10.040 .

Stanojlović, Miloš R., Guševac, Ivana, Grković, Ivana, Martinović, Jelena, Mitrović, Nataša Lj., Zarić, Marina, Horvat, Anica, Drakulić, Dunja R., "Effects of Chronic Cerebral Hypoperfusion and Low-Dose Progesterone Treatment on Apoptotic Processes, Expression and Subcellular Localization of Key Elements Within Akt and Erk Signaling Pathways in Rat Hippocampus" in Neuroscience, 311 (2015):308-321,
https://doi.org/10.1016/j.neuroscience.2015.10.040 . .

TY  - JOUR
AU  - Stanojlović, Miloš R.
AU  - Horvat, Anica
AU  - Guševac, Ivana
AU  - Grković, Ivana
AU  - Mitrović, Nataša Lj.
AU  - Buzadzic, I.
AU  - Drakulić, Dunja R.
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5445
AB  - To study time-dependent and gender-specific intracellular and biochemical mechanisms that lead to neurodegeneration due to moderate but persistent reduction of cerebral blood flow, adult male and female Wistar rats were divided into two main groups controls that underwent sham operation and animals subjected to permanent bilateral occlusion of common carotid arteries. Animals were sacrificed 3, 7 or 90 days following the insult. Expression of several apoptotic proteins in synaptic fractions along with Fluoro-Jade B staining and DNA fragmentation assay were used to estimate the apoptotic processes and potential neurodegeneration in cerebral cortex. Data suggest a time-specific increase of Bax as well as time- and gender-associated down-regulation in protein expression of Bcl-2, up-regulation of procaspase 3, accompanied with increased cleavage of procaspase 3 and PARP in synaptic terminals. Furthermore, time- but not gender-specific neurodegeneration was observed. Our findings support the concept of time- and gender-associated response to permanent bilateral occlusion of common carotid arteries, which would enable better understanding of the mechanisms underlying cerebral hypoperfusion.
T2  - Folia Biologica
T1  - Time Course of Cerebral Hypoperfusion-Induced Neurodegenerative Changes in the Cortex of Male and Female Rats
VL  - 60
IS  - 3
SP  - 123
EP  - 132
UR  - https://hdl.handle.net/21.15107/rcub_vinar_5445
ER  - 

@article{
author = "Stanojlović, Miloš R. and Horvat, Anica and Guševac, Ivana and Grković, Ivana and Mitrović, Nataša Lj. and Buzadzic, I. and Drakulić, Dunja R.",
year = "2014",
abstract = "To study time-dependent and gender-specific intracellular and biochemical mechanisms that lead to neurodegeneration due to moderate but persistent reduction of cerebral blood flow, adult male and female Wistar rats were divided into two main groups controls that underwent sham operation and animals subjected to permanent bilateral occlusion of common carotid arteries. Animals were sacrificed 3, 7 or 90 days following the insult. Expression of several apoptotic proteins in synaptic fractions along with Fluoro-Jade B staining and DNA fragmentation assay were used to estimate the apoptotic processes and potential neurodegeneration in cerebral cortex. Data suggest a time-specific increase of Bax as well as time- and gender-associated down-regulation in protein expression of Bcl-2, up-regulation of procaspase 3, accompanied with increased cleavage of procaspase 3 and PARP in synaptic terminals. Furthermore, time- but not gender-specific neurodegeneration was observed. Our findings support the concept of time- and gender-associated response to permanent bilateral occlusion of common carotid arteries, which would enable better understanding of the mechanisms underlying cerebral hypoperfusion.",
journal = "Folia Biologica",
title = "Time Course of Cerebral Hypoperfusion-Induced Neurodegenerative Changes in the Cortex of Male and Female Rats",
volume = "60",
number = "3",
pages = "123-132",
url = "https://hdl.handle.net/21.15107/rcub_vinar_5445"
}

Stanojlović, M. R., Horvat, A., Guševac, I., Grković, I., Mitrović, N. Lj., Buzadzic, I.,& Drakulić, D. R.. (2014). Time Course of Cerebral Hypoperfusion-Induced Neurodegenerative Changes in the Cortex of Male and Female Rats. in Folia Biologica, 60(3), 123-132.
https://hdl.handle.net/21.15107/rcub_vinar_5445

Stanojlović MR, Horvat A, Guševac I, Grković I, Mitrović NL, Buzadzic I, Drakulić DR. Time Course of Cerebral Hypoperfusion-Induced Neurodegenerative Changes in the Cortex of Male and Female Rats. in Folia Biologica. 2014;60(3):123-132.
https://hdl.handle.net/21.15107/rcub_vinar_5445 .

Stanojlović, Miloš R., Horvat, Anica, Guševac, Ivana, Grković, Ivana, Mitrović, Nataša Lj., Buzadzic, I., Drakulić, Dunja R., "Time Course of Cerebral Hypoperfusion-Induced Neurodegenerative Changes in the Cortex of Male and Female Rats" in Folia Biologica, 60, no. 3 (2014):123-132,
https://hdl.handle.net/21.15107/rcub_vinar_5445 .

TY  - JOUR
AU  - Stanojlović, Miloš R.
AU  - Guševac, Ivana
AU  - Grković, Ivana
AU  - Mitrović, Nataša Lj.
AU  - Horvat, Anica
AU  - Drakulić, Dunja R.
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/301
AB  - Although the model of cerebral hypoperfusion in rats has been a matter of many investigations over the years, the exact intracellular and biochemical mechanisms that lead to neuron loss and memory decline have not been clearly identified. In the current study, we examined whether cerebral hypoperfusion causes changes in hippocampal protein expression of apoptotic markers in the synaptosomal fraction and neurodegeneration in a time-dependent and sex-specific manner. Adult male and female Wistar rats were divided into two main groups, controls that underwent sham operation, and animals subjected to permanent bilateral occlusion of common carotid arteries. Both male and female rats were killed 3, 7 or 90 days following the insult. The obtained results indicate that the peak of processes that lead to apoptosis occured on postoperative day 7 and that they were more prominent in males, indicating that neuroprotective effects of certain substances (planned for future experiments), should be tested at this time point.
T2  - Archives of Biological Sciences
T1  - Time-Related Sex Diffrences in Cerebral Hypoperfusion-Induced Brain Injury
VL  - 66
IS  - 4
SP  - 1673
EP  - 1680
DO  - 10.2298/ABS1404673S
ER  - 

@article{
author = "Stanojlović, Miloš R. and Guševac, Ivana and Grković, Ivana and Mitrović, Nataša Lj. and Horvat, Anica and Drakulić, Dunja R.",
year = "2014",
abstract = "Although the model of cerebral hypoperfusion in rats has been a matter of many investigations over the years, the exact intracellular and biochemical mechanisms that lead to neuron loss and memory decline have not been clearly identified. In the current study, we examined whether cerebral hypoperfusion causes changes in hippocampal protein expression of apoptotic markers in the synaptosomal fraction and neurodegeneration in a time-dependent and sex-specific manner. Adult male and female Wistar rats were divided into two main groups, controls that underwent sham operation, and animals subjected to permanent bilateral occlusion of common carotid arteries. Both male and female rats were killed 3, 7 or 90 days following the insult. The obtained results indicate that the peak of processes that lead to apoptosis occured on postoperative day 7 and that they were more prominent in males, indicating that neuroprotective effects of certain substances (planned for future experiments), should be tested at this time point.",
journal = "Archives of Biological Sciences",
title = "Time-Related Sex Diffrences in Cerebral Hypoperfusion-Induced Brain Injury",
volume = "66",
number = "4",
pages = "1673-1680",
doi = "10.2298/ABS1404673S"
}

Stanojlović, M. R., Guševac, I., Grković, I., Mitrović, N. Lj., Horvat, A.,& Drakulić, D. R.. (2014). Time-Related Sex Diffrences in Cerebral Hypoperfusion-Induced Brain Injury. in Archives of Biological Sciences, 66(4), 1673-1680.
https://doi.org/10.2298/ABS1404673S

Stanojlović MR, Guševac I, Grković I, Mitrović NL, Horvat A, Drakulić DR. Time-Related Sex Diffrences in Cerebral Hypoperfusion-Induced Brain Injury. in Archives of Biological Sciences. 2014;66(4):1673-1680.
doi:10.2298/ABS1404673S .

Stanojlović, Miloš R., Guševac, Ivana, Grković, Ivana, Mitrović, Nataša Lj., Horvat, Anica, Drakulić, Dunja R., "Time-Related Sex Diffrences in Cerebral Hypoperfusion-Induced Brain Injury" in Archives of Biological Sciences, 66, no. 4 (2014):1673-1680,
https://doi.org/10.2298/ABS1404673S . .