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

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

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

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

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

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

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

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

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

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

TY  - 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  - Nikolić, Biljana
AU  - Martinović, Jelena
AU  - Matić, Milan
AU  - Stefanović, Đorđe
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8377
AB  - BACKGROUND: Different variables determine the performance of cyclists, which brings up the question how these parameters may help in their classification by specialty. The aim of the study was to determine differences in cardiorespiratory parameters of male cyclists according to their specialty: flat riders (N.=21), hill riders (N.=35), or sprinters (N.=20) and obtain the multivariate model for further cyclists classification by specialties, based on selected variables. METHODS: Seventeen variables were measured at submaximal and maximum load on the cycle ergometer Cosmed E 400HK (Cosmed, Rome, Italy) (initial 100 W with 25-W increase, 90-100 rpm). Multivariate discriminant analysis was used to determine which variables group cyclists within their specialty, and to predict which variables can direct cyclists to a particular specialty. RESULTS: Among nine variables that statistically contribute to the discriminant power of the model, achieved power on the anaerobic threshold and the produced CO 2 had the biggest impact. The obtained discriminatory model correctly classified 91.43% of flat riders, 85.71% of hill riders, while sprinters were classified completely correct (100%), i.e. 92.10% of examinees were correctly classified, which point out the strength of the discriminatory model. CONCLUSIONS: Respiratory indicators mostly contribute to the discriminant power of the model, which may significantly contribute to training practice and laboratory tests in future. © 2018 EDIZIONI MINERVA MEDICA.
T2  - The Journal of Sports Medicine and Physical Fitness
T1  - Discriminant analysis of cardiovascular and respiratory variables for classification of road cyclists by specialty
VL  - 59
IS  - 6
SP  - 955
EP  - 961
DO  - 10.23736/S0022-4707.18.08478-5
ER  - 

@article{
author = "Nikolić, Biljana and Martinović, Jelena and Matić, Milan and Stefanović, Đorđe",
year = "2019",
abstract = "BACKGROUND: Different variables determine the performance of cyclists, which brings up the question how these parameters may help in their classification by specialty. The aim of the study was to determine differences in cardiorespiratory parameters of male cyclists according to their specialty: flat riders (N.=21), hill riders (N.=35), or sprinters (N.=20) and obtain the multivariate model for further cyclists classification by specialties, based on selected variables. METHODS: Seventeen variables were measured at submaximal and maximum load on the cycle ergometer Cosmed E 400HK (Cosmed, Rome, Italy) (initial 100 W with 25-W increase, 90-100 rpm). Multivariate discriminant analysis was used to determine which variables group cyclists within their specialty, and to predict which variables can direct cyclists to a particular specialty. RESULTS: Among nine variables that statistically contribute to the discriminant power of the model, achieved power on the anaerobic threshold and the produced CO 2 had the biggest impact. The obtained discriminatory model correctly classified 91.43% of flat riders, 85.71% of hill riders, while sprinters were classified completely correct (100%), i.e. 92.10% of examinees were correctly classified, which point out the strength of the discriminatory model. CONCLUSIONS: Respiratory indicators mostly contribute to the discriminant power of the model, which may significantly contribute to training practice and laboratory tests in future. © 2018 EDIZIONI MINERVA MEDICA.",
journal = "The Journal of Sports Medicine and Physical Fitness",
title = "Discriminant analysis of cardiovascular and respiratory variables for classification of road cyclists by specialty",
volume = "59",
number = "6",
pages = "955-961",
doi = "10.23736/S0022-4707.18.08478-5"
}

Nikolić, B., Martinović, J., Matić, M.,& Stefanović, Đ.. (2019). Discriminant analysis of cardiovascular and respiratory variables for classification of road cyclists by specialty. in The Journal of Sports Medicine and Physical Fitness, 59(6), 955-961.
https://doi.org/10.23736/S0022-4707.18.08478-5

Nikolić B, Martinović J, Matić M, Stefanović Đ. Discriminant analysis of cardiovascular and respiratory variables for classification of road cyclists by specialty. in The Journal of Sports Medicine and Physical Fitness. 2019;59(6):955-961.
doi:10.23736/S0022-4707.18.08478-5 .

Nikolić, Biljana, Martinović, Jelena, Matić, Milan, Stefanović, Đorđe, "Discriminant analysis of cardiovascular and respiratory variables for classification of road cyclists by specialty" in The Journal of Sports Medicine and Physical Fitness, 59, no. 6 (2019):955-961,
https://doi.org/10.23736/S0022-4707.18.08478-5 . .

TY  - JOUR
AU  - Grković, Ivana
AU  - Drakulić, Dunja R.
AU  - Martinović, Jelena
AU  - Mitrović, Nataša Lj.
PY  - 2019
UR  - http://www.eurekaselect.com/node/152565/article
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7758
AB  - Extracellular adenine nucleotides and nucleosides, such as ATP and adenosine, are among the most recently identified and least investigated diffusible signaling factors that contribute to the structural and functional remodeling of the brain, both during embryonic and postnatal development. Their levels in the extracellular milieu are tightly controlled by various ectonucleotidases: ectonucleotide pyrophosphatase/phosphodiesterases (E-NPP), alkaline phosphatases (AP), ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) and ecto-5'-nucleotidase (eN). During central nervous system development and in adulthood all ectonucleotidases have diverse expression pattern, cell specific localization and function. Formation, maturation, and refinement of synaptic contacts are influenced by neurotransmitters and neuromodulators, and control of extracellular adenine nucleotide levels by ectonucleotidases are important for understanding the role of purinergic signaling in developing tissues and potential targets in developmental disorders such as autism.
T2  - Current Neuropharmacology
T1  - Role of Ectonucleotidases in the Synapse Formation During Brain Development: Physiological and Pathological Implications
VL  - 17
IS  - 1
SP  - 84
EP  - 98
DO  - 10.2174/1570159X15666170518151541
ER  - 

@article{
author = "Grković, Ivana and Drakulić, Dunja R. and Martinović, Jelena and Mitrović, Nataša Lj.",
year = "2019",
abstract = "Extracellular adenine nucleotides and nucleosides, such as ATP and adenosine, are among the most recently identified and least investigated diffusible signaling factors that contribute to the structural and functional remodeling of the brain, both during embryonic and postnatal development. Their levels in the extracellular milieu are tightly controlled by various ectonucleotidases: ectonucleotide pyrophosphatase/phosphodiesterases (E-NPP), alkaline phosphatases (AP), ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) and ecto-5'-nucleotidase (eN). During central nervous system development and in adulthood all ectonucleotidases have diverse expression pattern, cell specific localization and function. Formation, maturation, and refinement of synaptic contacts are influenced by neurotransmitters and neuromodulators, and control of extracellular adenine nucleotide levels by ectonucleotidases are important for understanding the role of purinergic signaling in developing tissues and potential targets in developmental disorders such as autism.",
journal = "Current Neuropharmacology",
title = "Role of Ectonucleotidases in the Synapse Formation During Brain Development: Physiological and Pathological Implications",
volume = "17",
number = "1",
pages = "84-98",
doi = "10.2174/1570159X15666170518151541"
}

Grković, I., Drakulić, D. R., Martinović, J.,& Mitrović, N. Lj.. (2019). Role of Ectonucleotidases in the Synapse Formation During Brain Development: Physiological and Pathological Implications. in Current Neuropharmacology, 17(1), 84-98.
https://doi.org/10.2174/1570159X15666170518151541

Grković I, Drakulić DR, Martinović J, Mitrović NL. Role of Ectonucleotidases in the Synapse Formation During Brain Development: Physiological and Pathological Implications. in Current Neuropharmacology. 2019;17(1):84-98.
doi:10.2174/1570159X15666170518151541 .

Grković, Ivana, Drakulić, Dunja R., Martinović, Jelena, Mitrović, Nataša Lj., "Role of Ectonucleotidases in the Synapse Formation During Brain Development: Physiological and Pathological Implications" in Current Neuropharmacology, 17, no. 1 (2019):84-98,
https://doi.org/10.2174/1570159X15666170518151541 . .

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TY  - JOUR
AU  - Grković, Ivana
AU  - Bjelobaba, Ivana
AU  - Mitrović, Nataša Lj.
AU  - Lavrnja, Irena
AU  - Drakulić, Dunja R.
AU  - Martinović, Jelena
AU  - Stanojlović, Miloš R.
AU  - Horvat, Anica
AU  - Nedeljković, Nadežda
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1289
AB  - Nucleoside triphosphate diphosphohydrolase3 (NTPDase3) is membrane-bound ecto-enzyme which hydrolyzes extracellular ATP, thus modulating the function of purinergic receptors and the pattern of purinergic signaling. Here we analyzed the developmental expression of NTPDase3 in female hypothalamus, cerebral cortex and hippocampal formation at different postnatal ages (PD7-PD90) by qRT-PCR and immunohistochemistry. In hypothalamus and hippocampus, a similar developmental profile was seen: NTPDase3 gene expression was stable during postnatal development and increased in adults. In the cortex, upregulation of NTPDase3 mRNA expression was seen at PD15 and further increase was evidenced in adults. Immunohistochemical analysis at PD7 revealed faint neuronal NTPDase3 localization in a dorsal hypothalamus. The immunoreactivity (ir) gradually increased in PD15 and PD20, in clusters of cells in the lateral, ventral and dorsomedial hypothalamus. Furthermore, in PD20 animals, NTPDase3-ir was detected on short fibers in the posterior hypothalamic area, while in PD30 the fibers appeared progressively longer and markedly varicose. In adults, the strongest NTPDase3-ir was observed in collections of cells in dorsomedial hypothalamic nucleus, dorsal and lateral hypothalamus and in several thalamic areas, whereas the varicose fibers traversed entire diencephalon, particularly paraventricular thalamic nucleus, ventromedial and dorsomedial hypothalamic nuclei, the arcuate nucleus and the prefornical part of the lateral hypothalamus. The presumably ascending NTPDase3-ir fibers were first observed in PD20; their density and the varicose appearance increased until the adulthood. Prominent enhancement of NTPDase3-ir in the hypothalamus coincides with age when animals acquire diurnal rhythms of sleeping and feeding, supporting the hypothesis that this enzyme may be involved in regulation of homeostatic functions. (C) 2016 Elsevier B.V. All rights reserved.
T2  - Journal of Chemical Neuroanatomy
T1  - Expression of ecto-nucleoside triphosphate diphosphohydrolase3 (NTPDase3) in the female rat brain during postnatal development
VL  - 77
SP  - 10
EP  - 18
DO  - 10.1016/j.jchemneu.2016.04.001
ER  - 

@article{
author = "Grković, Ivana and Bjelobaba, Ivana and Mitrović, Nataša Lj. and Lavrnja, Irena and Drakulić, Dunja R. and Martinović, Jelena and Stanojlović, Miloš R. and Horvat, Anica and Nedeljković, Nadežda",
year = "2016",
abstract = "Nucleoside triphosphate diphosphohydrolase3 (NTPDase3) is membrane-bound ecto-enzyme which hydrolyzes extracellular ATP, thus modulating the function of purinergic receptors and the pattern of purinergic signaling. Here we analyzed the developmental expression of NTPDase3 in female hypothalamus, cerebral cortex and hippocampal formation at different postnatal ages (PD7-PD90) by qRT-PCR and immunohistochemistry. In hypothalamus and hippocampus, a similar developmental profile was seen: NTPDase3 gene expression was stable during postnatal development and increased in adults. In the cortex, upregulation of NTPDase3 mRNA expression was seen at PD15 and further increase was evidenced in adults. Immunohistochemical analysis at PD7 revealed faint neuronal NTPDase3 localization in a dorsal hypothalamus. The immunoreactivity (ir) gradually increased in PD15 and PD20, in clusters of cells in the lateral, ventral and dorsomedial hypothalamus. Furthermore, in PD20 animals, NTPDase3-ir was detected on short fibers in the posterior hypothalamic area, while in PD30 the fibers appeared progressively longer and markedly varicose. In adults, the strongest NTPDase3-ir was observed in collections of cells in dorsomedial hypothalamic nucleus, dorsal and lateral hypothalamus and in several thalamic areas, whereas the varicose fibers traversed entire diencephalon, particularly paraventricular thalamic nucleus, ventromedial and dorsomedial hypothalamic nuclei, the arcuate nucleus and the prefornical part of the lateral hypothalamus. The presumably ascending NTPDase3-ir fibers were first observed in PD20; their density and the varicose appearance increased until the adulthood. Prominent enhancement of NTPDase3-ir in the hypothalamus coincides with age when animals acquire diurnal rhythms of sleeping and feeding, supporting the hypothesis that this enzyme may be involved in regulation of homeostatic functions. (C) 2016 Elsevier B.V. All rights reserved.",
journal = "Journal of Chemical Neuroanatomy",
title = "Expression of ecto-nucleoside triphosphate diphosphohydrolase3 (NTPDase3) in the female rat brain during postnatal development",
volume = "77",
pages = "10-18",
doi = "10.1016/j.jchemneu.2016.04.001"
}

Grković, I., Bjelobaba, I., Mitrović, N. Lj., Lavrnja, I., Drakulić, D. R., Martinović, J., Stanojlović, M. R., Horvat, A.,& Nedeljković, N.. (2016). Expression of ecto-nucleoside triphosphate diphosphohydrolase3 (NTPDase3) in the female rat brain during postnatal development. in Journal of Chemical Neuroanatomy, 77, 10-18.
https://doi.org/10.1016/j.jchemneu.2016.04.001

Grković I, Bjelobaba I, Mitrović NL, Lavrnja I, Drakulić DR, Martinović J, Stanojlović MR, Horvat A, Nedeljković N. Expression of ecto-nucleoside triphosphate diphosphohydrolase3 (NTPDase3) in the female rat brain during postnatal development. in Journal of Chemical Neuroanatomy. 2016;77:10-18.
doi:10.1016/j.jchemneu.2016.04.001 .

Grković, Ivana, Bjelobaba, Ivana, Mitrović, Nataša Lj., Lavrnja, Irena, Drakulić, Dunja R., Martinović, Jelena, Stanojlović, Miloš R., Horvat, Anica, Nedeljković, Nadežda, "Expression of ecto-nucleoside triphosphate diphosphohydrolase3 (NTPDase3) in the female rat brain during postnatal development" in Journal of Chemical Neuroanatomy, 77 (2016):10-18,
https://doi.org/10.1016/j.jchemneu.2016.04.001 . .

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

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

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

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

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

TY  - JOUR
AU  - Stanojlović, Miloš R.
AU  - 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 . .