Cellular and molecular basis of neuroinflamation: potential targets for translational medicine and therapy

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Cellular and molecular basis of neuroinflamation: potential targets for translational medicine and therapy (en)
Ћелијска и молекулска основа неуроинфламације: потенцијала циљна места за транслациону медицину и терапију (sr)
Ćelijska i molekulska osnova neuroinflamacije: potencijala ciljna mesta za translacionu medicinu i terapiju (sr_RS)
Authors

Publications

Increased plasma phosphatidylcholine/lysophosphatidylcholine ratios in patients with Parkinson's disease

Miletić Vukajlović, Jadranka; Drakulić, Dunja R.; Pejić, Snežana; Ilić, Tihomir V.; Stefanović, Aleksandra; Petković, Marijana; Schiller, Jürgen

(2020)

TY  - JOUR
AU  - Miletić Vukajlović, Jadranka
AU  - Drakulić, Dunja R.
AU  - Pejić, Snežana
AU  - Ilić, Tihomir V.
AU  - Stefanović, Aleksandra
AU  - Petković, Marijana
AU  - Schiller, Jürgen
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8476
AB  - Rationale: Changes in lipid composition might be associated with the onset and progression of various neurodegenerative diseases. Herein, we investigated the changes in the plasma phosphatidylcholine (PC)/lysophosphatidylcholine (LPC) ratios in patients with Parkinson's disease (PD) in comparison with healthy subjects and their correlation with clinico-pathological features. Methods: The study included 10 controls and 25 patients with PD. All patients were assigned to groups based on clinico-pathological characteristics (gender, age at examination, duration of disease and Hoehn and Yahr (H&Y) stage). The analysis of the PC/LPC intensity ratios in plasma lipid extracts was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results: PD patients exhibited an increased PC/LPC intensity ratio in comparison with the control group of healthy subjects. Furthermore, the investigated ratio was shown to be correlated with clinico-pathological parameters, in particular with H&Y stage and disease duration. The PC/LPC intensity ratio in plasma samples of PD patients was found to be elevated in all examined H&Y stages and throughout the disease duration. Conclusions: To our knowledge, this is the first study examining the PC/LPC ratios in plasma of patients with PD and illustrating their correlation with clinico-pathological features. Although the presented results may be considered as preliminary due to the limited number of participants, the observed alterations of PC/LPC ratios in plasma might be a first step in the characterization of plasma lipid changes in PD patients and an indicator of lipid reconfiguration. © 2019 John Wiley & Sons, Ltd.
T2  - Rapid Communications in Mass Spectrometry
T1  - Increased plasma phosphatidylcholine/lysophosphatidylcholine ratios in patients with Parkinson's disease
VL  - 34
IS  - 4
DO  - 10.1002/rcm.8595
ER  - 
@article{
author = "Miletić Vukajlović, Jadranka and Drakulić, Dunja R. and Pejić, Snežana and Ilić, Tihomir V. and Stefanović, Aleksandra and Petković, Marijana and Schiller, Jürgen",
year = "2020",
abstract = "Rationale: Changes in lipid composition might be associated with the onset and progression of various neurodegenerative diseases. Herein, we investigated the changes in the plasma phosphatidylcholine (PC)/lysophosphatidylcholine (LPC) ratios in patients with Parkinson's disease (PD) in comparison with healthy subjects and their correlation with clinico-pathological features. Methods: The study included 10 controls and 25 patients with PD. All patients were assigned to groups based on clinico-pathological characteristics (gender, age at examination, duration of disease and Hoehn and Yahr (H&Y) stage). The analysis of the PC/LPC intensity ratios in plasma lipid extracts was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results: PD patients exhibited an increased PC/LPC intensity ratio in comparison with the control group of healthy subjects. Furthermore, the investigated ratio was shown to be correlated with clinico-pathological parameters, in particular with H&Y stage and disease duration. The PC/LPC intensity ratio in plasma samples of PD patients was found to be elevated in all examined H&Y stages and throughout the disease duration. Conclusions: To our knowledge, this is the first study examining the PC/LPC ratios in plasma of patients with PD and illustrating their correlation with clinico-pathological features. Although the presented results may be considered as preliminary due to the limited number of participants, the observed alterations of PC/LPC ratios in plasma might be a first step in the characterization of plasma lipid changes in PD patients and an indicator of lipid reconfiguration. © 2019 John Wiley & Sons, Ltd.",
journal = "Rapid Communications in Mass Spectrometry",
title = "Increased plasma phosphatidylcholine/lysophosphatidylcholine ratios in patients with Parkinson's disease",
volume = "34",
number = "4",
doi = "10.1002/rcm.8595"
}
Miletić Vukajlović, J., Drakulić, D. R., Pejić, S., Ilić, T. V., Stefanović, A., Petković, M.,& Schiller, J.. (2020). Increased plasma phosphatidylcholine/lysophosphatidylcholine ratios in patients with Parkinson's disease. in Rapid Communications in Mass Spectrometry, 34(4).
https://doi.org/10.1002/rcm.8595
Miletić Vukajlović J, Drakulić DR, Pejić S, Ilić TV, Stefanović A, Petković M, Schiller J. Increased plasma phosphatidylcholine/lysophosphatidylcholine ratios in patients with Parkinson's disease. in Rapid Communications in Mass Spectrometry. 2020;34(4).
doi:10.1002/rcm.8595 .
Miletić Vukajlović, Jadranka, Drakulić, Dunja R., Pejić, Snežana, Ilić, Tihomir V., Stefanović, Aleksandra, Petković, Marijana, Schiller, Jürgen, "Increased plasma phosphatidylcholine/lysophosphatidylcholine ratios in patients with Parkinson's disease" in Rapid Communications in Mass Spectrometry, 34, no. 4 (2020),
https://doi.org/10.1002/rcm.8595 . .
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Progesterone Protects Prefrontal Cortex in Rat Model of Permanent Bilateral Common Carotid Occlusion via Progesterone Receptors and Akt/Erk/eNOS

Stanojlović, Miloš R.; Guševac Stojanović, Ivana; Zarić, Marina; Martinović, Jelena; Mitrović, Nataša Lj.; Grković, Ivana; Drakulić, Dunja R.

(2020)

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 . .
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Estradiol induces synaptic rearrangements

Grković, Ivana; Mitrović, Nataša Lj.

(2020)

TY  - CHAP
AU  - Grković, Ivana
AU  - Mitrović, Nataša Lj.
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9056
AB  - 17β-Estradiol (E2) is a potent steroid hormone of both gonadal and neuronal origin that exerts profound effects on neuroplasticity in several brain regions. Dendritic spine and synapse formation and rearrangements are modulated and mediated by estrogens. In this chapter, we highlighted the essential background concerning the effects of E2 on synaptic rearrangements accompanied by synaptic plasticity in E2-sensitive brain regions that mediate learning and memory, i.e., cortex and hippocampus. We also address details of the molecular mechanisms underlying E2 regulation of spine dynamics. The proposed models of action of E2 overlaps with that for well-established synaptic modulators, such as adenosine. Thus, the possible synergistic effects of those two molecules in respect to synaptic rearrangement and plasticity were presented.
T2  - Vitamins and Hormones
T1  - Estradiol induces synaptic rearrangements
VL  - 114
SP  - 233
EP  - 256
DO  - 10.1016/bs.vh.2020.04.006
ER  - 
@inbook{
author = "Grković, Ivana and Mitrović, Nataša Lj.",
year = "2020",
abstract = "17β-Estradiol (E2) is a potent steroid hormone of both gonadal and neuronal origin that exerts profound effects on neuroplasticity in several brain regions. Dendritic spine and synapse formation and rearrangements are modulated and mediated by estrogens. In this chapter, we highlighted the essential background concerning the effects of E2 on synaptic rearrangements accompanied by synaptic plasticity in E2-sensitive brain regions that mediate learning and memory, i.e., cortex and hippocampus. We also address details of the molecular mechanisms underlying E2 regulation of spine dynamics. The proposed models of action of E2 overlaps with that for well-established synaptic modulators, such as adenosine. Thus, the possible synergistic effects of those two molecules in respect to synaptic rearrangement and plasticity were presented.",
journal = "Vitamins and Hormones",
booktitle = "Estradiol induces synaptic rearrangements",
volume = "114",
pages = "233-256",
doi = "10.1016/bs.vh.2020.04.006"
}
Grković, I.,& Mitrović, N. Lj.. (2020). Estradiol induces synaptic rearrangements. in Vitamins and Hormones, 114, 233-256.
https://doi.org/10.1016/bs.vh.2020.04.006
Grković I, Mitrović NL. Estradiol induces synaptic rearrangements. in Vitamins and Hormones. 2020;114:233-256.
doi:10.1016/bs.vh.2020.04.006 .
Grković, Ivana, Mitrović, Nataša Lj., "Estradiol induces synaptic rearrangements" in Vitamins and Hormones, 114 (2020):233-256,
https://doi.org/10.1016/bs.vh.2020.04.006 . .
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Antioxidant status and clinicopathological parameters in patients with Parkinson's disease

Miletić Vukajlović, Jadranka; Pejić, Snežana; Todorović, Ana; Valenta-Šobot, Ana; Drakulić, Dunja R.; Pavlović, Ivan; Stefanović, Aleksandra; Prostran, Milica; Ilić, Tihomir V.; Stojanov, Marina

(2019)

TY  - JOUR
AU  - Miletić Vukajlović, Jadranka
AU  - Pejić, Snežana
AU  - Todorović, Ana
AU  - Valenta-Šobot, Ana
AU  - Drakulić, Dunja R.
AU  - Pavlović, Ivan
AU  - Stefanović, Aleksandra
AU  - Prostran, Milica
AU  - Ilić, Tihomir V.
AU  - Stojanov, Marina
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8407
AB  - Backgroun / Aim. Constant production of free radicals and antioxidants (AO) in the cell is a part of normal cellular function. Their imbalance might take a part in pathophysiology of many diseases, including Parkinson’s disease (PD). Evaluation of the disease status, prooxidant-antioxidant balance (PAB) and antioxidants are being widely estimated. The aim of this study was to examine potential interaction between several AO variables (GSH, SOD, CAT and PAB) and clinicopathological features of patients with PD, particularly Hoehn and Yahr (H&Y) stage. Methods. A multivariate analysis of variance (MANOVA) was conducted to test the hypothesis of the mean differences between clinicopathological characteristics (gender, age at examination, duration of the disease, and H&Y stage) and AO variables, compared with age/sex matched healthy controls. The study included 91 patients with idiopatic PD patients and 20 healthy controls. Results. The multivariate effect size was estimated at 0.269, p <0.001, implying that 27.0% of the variance of the dependent variables was accounted for H&Y stage. Univariate tests showed that there were significant differences (p <0.001) across the H&Y stage on all AO variables. The H&Y stage remained significant predictor after controlling for the second variable, the disease duration (p <0.001, η2 = 0.249), and there were still significant differences across the H&Y stage on all variables, with effect size ( η2) ranging from 0.132, p =0.011 (lnGSH) to the still high values of 0.535 (lnPAB), 0.627 (lnSOD) and 0.964 (lnCAT). Conclusion. The results indicate that higher level of oxidative stress in blood of PD patients is possibly related to PD stage. Along with reduction of SOD and GSH level, CAT activity was elevated in comparison to healthy subjects. Furthermore, Pwas shifted toward oxidative stress.
T2  - Vojnosanitetski pregled
T1  - Antioxidant status and clinicopathological parameters in patients with Parkinson's disease
VL  - 77
IS  - 7
SP  - 724
EP  - 730
DO  - 10.2298/VSP180718148M
ER  - 
@article{
author = "Miletić Vukajlović, Jadranka and Pejić, Snežana and Todorović, Ana and Valenta-Šobot, Ana and Drakulić, Dunja R. and Pavlović, Ivan and Stefanović, Aleksandra and Prostran, Milica and Ilić, Tihomir V. and Stojanov, Marina",
year = "2019",
abstract = "Backgroun / Aim. Constant production of free radicals and antioxidants (AO) in the cell is a part of normal cellular function. Their imbalance might take a part in pathophysiology of many diseases, including Parkinson’s disease (PD). Evaluation of the disease status, prooxidant-antioxidant balance (PAB) and antioxidants are being widely estimated. The aim of this study was to examine potential interaction between several AO variables (GSH, SOD, CAT and PAB) and clinicopathological features of patients with PD, particularly Hoehn and Yahr (H&Y) stage. Methods. A multivariate analysis of variance (MANOVA) was conducted to test the hypothesis of the mean differences between clinicopathological characteristics (gender, age at examination, duration of the disease, and H&Y stage) and AO variables, compared with age/sex matched healthy controls. The study included 91 patients with idiopatic PD patients and 20 healthy controls. Results. The multivariate effect size was estimated at 0.269, p <0.001, implying that 27.0% of the variance of the dependent variables was accounted for H&Y stage. Univariate tests showed that there were significant differences (p <0.001) across the H&Y stage on all AO variables. The H&Y stage remained significant predictor after controlling for the second variable, the disease duration (p <0.001, η2 = 0.249), and there were still significant differences across the H&Y stage on all variables, with effect size ( η2) ranging from 0.132, p =0.011 (lnGSH) to the still high values of 0.535 (lnPAB), 0.627 (lnSOD) and 0.964 (lnCAT). Conclusion. The results indicate that higher level of oxidative stress in blood of PD patients is possibly related to PD stage. Along with reduction of SOD and GSH level, CAT activity was elevated in comparison to healthy subjects. Furthermore, Pwas shifted toward oxidative stress.",
journal = "Vojnosanitetski pregled",
title = "Antioxidant status and clinicopathological parameters in patients with Parkinson's disease",
volume = "77",
number = "7",
pages = "724-730",
doi = "10.2298/VSP180718148M"
}
Miletić Vukajlović, J., Pejić, S., Todorović, A., Valenta-Šobot, A., Drakulić, D. R., Pavlović, I., Stefanović, A., Prostran, M., Ilić, T. V.,& Stojanov, M.. (2019). Antioxidant status and clinicopathological parameters in patients with Parkinson's disease. in Vojnosanitetski pregled, 77(7), 724-730.
https://doi.org/10.2298/VSP180718148M
Miletić Vukajlović J, Pejić S, Todorović A, Valenta-Šobot A, Drakulić DR, Pavlović I, Stefanović A, Prostran M, Ilić TV, Stojanov M. Antioxidant status and clinicopathological parameters in patients with Parkinson's disease. in Vojnosanitetski pregled. 2019;77(7):724-730.
doi:10.2298/VSP180718148M .
Miletić Vukajlović, Jadranka, Pejić, Snežana, Todorović, Ana, Valenta-Šobot, Ana, Drakulić, Dunja R., Pavlović, Ivan, Stefanović, Aleksandra, Prostran, Milica, Ilić, Tihomir V., Stojanov, Marina, "Antioxidant status and clinicopathological parameters in patients with Parkinson's disease" in Vojnosanitetski pregled, 77, no. 7 (2019):724-730,
https://doi.org/10.2298/VSP180718148M . .
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Molecular Alterations and Effects of Acute Dehydroepiandrosterone Treatment Following Brief Bilateral Common Carotid Artery Occlusion: Relevance to Transient Ischemic Attack

Zarić, Marina; Drakulić, Dunja R.; Dragić, Milorad; Guševac Stojanović, Ivana; Mitrović, Nataša Lj.; Grković, Ivana; Martinović, Jelena

(2019)

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 . .
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Spatial Distribution and Expression of Ectonucleotidases in Rat Hippocampus After Removal of Ovaries and Estradiol Replacement

Grković, Ivana; Mitrović, Nataša Lj.; Dragić, Milorad; Adžić, Marija; Drakulić, Dunja R.; Nedeljković, Nadežda

(2019)

TY  - JOUR
AU  - Grković, Ivana
AU  - Mitrović, Nataša Lj.
AU  - Dragić, Milorad
AU  - Adžić, Marija
AU  - Drakulić, Dunja R.
AU  - Nedeljković, Nadežda
PY  - 2019
UR  - http://link.springer.com/10.1007/s12035-018-1217-3
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8102
AB  - Purinergic signaling is the main synaptic and non-synaptic signaling system in brain. ATP acts as a fast excitatory transmitter, while adenosine sets a global inhibitory tone within hippocampal neuronal networks. ATP and adenosine are interconnected by ectonucleotidase enzymes, which convert ATP to adenosine. Existing data point to the converging roles of ovarian steroids and purinergic signaling in synapse formation and refinement and synapse activity in the hippocampus. Therefore, in the present study, we have used enzyme histochemistry and expression analysis to obtain data on spatial distribution and expression of ecto-enzymes NTPDase1, NTPDase2, and ecto-5-nucleotidase (eN) after removal of ovaries (OVX) and estradiol replacement (E2) in female rat hippocampus. The results show that target ectonucleotidases are predominantly localized in synapse-rich hippocampal layers. The most represented NTPDase in the hippocampal tissue is NTPDase2, being at the same time the mostly affected ectonucleotidase by OVX and E2. Specifically, OVX decreases the expression of NTPDase2 and eN, whereas E2 restores their expression to control level. Impact of OVX and E2 on ectonucleotidase expression was also examined in purified synaptosome (SYN) and gliosome (GLIO) fractions. Data reveal that SYN expresses NTPDase1 and NTPDase2, both of which are reduced following OVX and restored with E2. GLIO exhibits NTPDase2-mediated ATP hydrolysis, which falls in OVX, and recovers by E2. These changes in the activity occur without parallel changes in NTPDase2-protein abundance. The same holds for eN. The lack of correlation between NTPDase2 and eN activities and their respective protein abundances suggest a non-genomic mode of E2 action, which is studied further in primary astrocyte culture. Since ovarian steroids shape hippocampal synaptic networks and regulate ectonucleotidase activities, it is possible that cognitive deficits seen after ovary removal may arise from the loss of E2 modulatory actions on ectonucleotidase expression in the hippocampus.
T2  - Molecular Neurobiology
T2  - Molecular Neurobiology
T1  - Spatial Distribution and Expression of Ectonucleotidases in Rat Hippocampus After Removal of Ovaries and Estradiol Replacement
VL  - 56
IS  - 3
SP  - 1933
EP  - 1945
DO  - 10.1007/s12035-018-1217-3
ER  - 
@article{
author = "Grković, Ivana and Mitrović, Nataša Lj. and Dragić, Milorad and Adžić, Marija and Drakulić, Dunja R. and Nedeljković, Nadežda",
year = "2019",
abstract = "Purinergic signaling is the main synaptic and non-synaptic signaling system in brain. ATP acts as a fast excitatory transmitter, while adenosine sets a global inhibitory tone within hippocampal neuronal networks. ATP and adenosine are interconnected by ectonucleotidase enzymes, which convert ATP to adenosine. Existing data point to the converging roles of ovarian steroids and purinergic signaling in synapse formation and refinement and synapse activity in the hippocampus. Therefore, in the present study, we have used enzyme histochemistry and expression analysis to obtain data on spatial distribution and expression of ecto-enzymes NTPDase1, NTPDase2, and ecto-5-nucleotidase (eN) after removal of ovaries (OVX) and estradiol replacement (E2) in female rat hippocampus. The results show that target ectonucleotidases are predominantly localized in synapse-rich hippocampal layers. The most represented NTPDase in the hippocampal tissue is NTPDase2, being at the same time the mostly affected ectonucleotidase by OVX and E2. Specifically, OVX decreases the expression of NTPDase2 and eN, whereas E2 restores their expression to control level. Impact of OVX and E2 on ectonucleotidase expression was also examined in purified synaptosome (SYN) and gliosome (GLIO) fractions. Data reveal that SYN expresses NTPDase1 and NTPDase2, both of which are reduced following OVX and restored with E2. GLIO exhibits NTPDase2-mediated ATP hydrolysis, which falls in OVX, and recovers by E2. These changes in the activity occur without parallel changes in NTPDase2-protein abundance. The same holds for eN. The lack of correlation between NTPDase2 and eN activities and their respective protein abundances suggest a non-genomic mode of E2 action, which is studied further in primary astrocyte culture. Since ovarian steroids shape hippocampal synaptic networks and regulate ectonucleotidase activities, it is possible that cognitive deficits seen after ovary removal may arise from the loss of E2 modulatory actions on ectonucleotidase expression in the hippocampus.",
journal = "Molecular Neurobiology, Molecular Neurobiology",
title = "Spatial Distribution and Expression of Ectonucleotidases in Rat Hippocampus After Removal of Ovaries and Estradiol Replacement",
volume = "56",
number = "3",
pages = "1933-1945",
doi = "10.1007/s12035-018-1217-3"
}
Grković, I., Mitrović, N. Lj., Dragić, M., Adžić, M., Drakulić, D. R.,& Nedeljković, N.. (2019). Spatial Distribution and Expression of Ectonucleotidases in Rat Hippocampus After Removal of Ovaries and Estradiol Replacement. in Molecular Neurobiology, 56(3), 1933-1945.
https://doi.org/10.1007/s12035-018-1217-3
Grković I, Mitrović NL, Dragić M, Adžić M, Drakulić DR, Nedeljković N. Spatial Distribution and Expression of Ectonucleotidases in Rat Hippocampus After Removal of Ovaries and Estradiol Replacement. in Molecular Neurobiology. 2019;56(3):1933-1945.
doi:10.1007/s12035-018-1217-3 .
Grković, Ivana, Mitrović, Nataša Lj., Dragić, Milorad, Adžić, Marija, Drakulić, Dunja R., Nedeljković, Nadežda, "Spatial Distribution and Expression of Ectonucleotidases in Rat Hippocampus After Removal of Ovaries and Estradiol Replacement" in Molecular Neurobiology, 56, no. 3 (2019):1933-1945,
https://doi.org/10.1007/s12035-018-1217-3 . .
1
15
10
14

Application of Gray Level Co-Occurrence Matrix Analysis as a New Method for Enzyme Histochemistry Quantification

Dragić, Milorad; Zarić, Marina; Mitrović, Nataša Lj.; Nedeljković, Nadežda; Grković, Ivana

(2019)

TY  - JOUR
AU  - Dragić, Milorad
AU  - Zarić, Marina
AU  - Mitrović, Nataša Lj.
AU  - Nedeljković, Nadežda
AU  - Grković, Ivana
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8489
AB  - Enzyme histochemistry is a valuable histological method which provides a connection between morphology, activity, and spatial localization of investigated enzymes. Even though the method relies purely on arbitrary evaluations performed by the human eye, it is still wildly accepted and used in histo(patho)logy. Texture analysis emerged as an excellent tool for image quantification of subtle differences reflected in both spatial discrepancies and gray level values of pixels. The current study of texture analysis utilizes the gray-level co-occurrence matrix as a method for quantification of differences between ecto-5′-nucleotidase activities in healthy hippocampal tissue and tissue with marked neurodegeneration. We used the angular second moment, contrast (CON), correlation, inverse difference moment (INV), and entropy for texture analysis and receiver operating characteristic analysis with immunoblot and qualitative assessment of enzyme histochemistry as a validation. Our results strongly argue that co-occurrence matrix analysis could be used for the determination of fine differences in the enzyme activities with the possibility to ascribe those differences to regions or specific cell types. In addition, it emerged that INV and CON are especially useful parameters for this type of enzyme histochemistry analysis. We concluded that texture analysis is a reliable method for quantification of this descriptive technique, thus removing biases and adding it a quantitative dimension.
T2  - Microscopy and Microanalysis
T1  - Application of Gray Level Co-Occurrence Matrix Analysis as a New Method for Enzyme Histochemistry Quantification
VL  - 25
IS  - 3
SP  - 690
EP  - 698
DO  - 10.1017/S1431927618016306
ER  - 
@article{
author = "Dragić, Milorad and Zarić, Marina and Mitrović, Nataša Lj. and Nedeljković, Nadežda and Grković, Ivana",
year = "2019",
abstract = "Enzyme histochemistry is a valuable histological method which provides a connection between morphology, activity, and spatial localization of investigated enzymes. Even though the method relies purely on arbitrary evaluations performed by the human eye, it is still wildly accepted and used in histo(patho)logy. Texture analysis emerged as an excellent tool for image quantification of subtle differences reflected in both spatial discrepancies and gray level values of pixels. The current study of texture analysis utilizes the gray-level co-occurrence matrix as a method for quantification of differences between ecto-5′-nucleotidase activities in healthy hippocampal tissue and tissue with marked neurodegeneration. We used the angular second moment, contrast (CON), correlation, inverse difference moment (INV), and entropy for texture analysis and receiver operating characteristic analysis with immunoblot and qualitative assessment of enzyme histochemistry as a validation. Our results strongly argue that co-occurrence matrix analysis could be used for the determination of fine differences in the enzyme activities with the possibility to ascribe those differences to regions or specific cell types. In addition, it emerged that INV and CON are especially useful parameters for this type of enzyme histochemistry analysis. We concluded that texture analysis is a reliable method for quantification of this descriptive technique, thus removing biases and adding it a quantitative dimension.",
journal = "Microscopy and Microanalysis",
title = "Application of Gray Level Co-Occurrence Matrix Analysis as a New Method for Enzyme Histochemistry Quantification",
volume = "25",
number = "3",
pages = "690-698",
doi = "10.1017/S1431927618016306"
}
Dragić, M., Zarić, M., Mitrović, N. Lj., Nedeljković, N.,& Grković, I.. (2019). Application of Gray Level Co-Occurrence Matrix Analysis as a New Method for Enzyme Histochemistry Quantification. in Microscopy and Microanalysis, 25(3), 690-698.
https://doi.org/10.1017/S1431927618016306
Dragić M, Zarić M, Mitrović NL, Nedeljković N, Grković I. Application of Gray Level Co-Occurrence Matrix Analysis as a New Method for Enzyme Histochemistry Quantification. in Microscopy and Microanalysis. 2019;25(3):690-698.
doi:10.1017/S1431927618016306 .
Dragić, Milorad, Zarić, Marina, Mitrović, Nataša Lj., Nedeljković, Nadežda, Grković, Ivana, "Application of Gray Level Co-Occurrence Matrix Analysis as a New Method for Enzyme Histochemistry Quantification" in Microscopy and Microanalysis, 25, no. 3 (2019):690-698,
https://doi.org/10.1017/S1431927618016306 . .
3
12
7
11

Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats

Mitrović, Nataša Lj.; Dragić, Milorad; Zarić, Marina; Drakulić, Dunja R.; Nedeljković, Nadežda; Grković, Ivana

(2019)

TY  - JOUR
AU  - Mitrović, Nataša Lj.
AU  - Dragić, Milorad
AU  - Zarić, Marina
AU  - Drakulić, Dunja R.
AU  - Nedeljković, Nadežda
AU  - Grković, Ivana
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8497
AB  - Extracellular adenine nucleotides and nucleosides, such as adenosine-5'-triphosphate (ATP) and adenosine, are among least investigated signaling factors that participate in 17β-estradiol (E2)-mediated synaptic rearrangements in rodent hippocampus. Their levels in the extrasynaptic space are tightly controlled by ecto-nucleoside triphosphate diphosphohydrolases1-3 (NTPDase1-3)/ecto-5'-nucleotidase (eN) enzyme chain. Therefore, the aim of the present study was to get closer insight in the E2-induced decrease in NTPDase and eN activity in the hippocampal synaptic compartment of male rats and to identify estradiol receptors (ERs i.e. ERα, ERβ or GPER1) responsible for the observed effects of E2. In this study we show indiscriminate participation of estradiol receptor α (ERα), -β (ERβ) and G- protein coupled estrogen receptor 1 (GPER1) in the mediation of E2 actions in hippocampal synaptosomes of male rats. Synaptic NTPDase1-3 activities are modulated only through activation of ERβ, while activation of ERα, -β and/or non-classical GPER1 decreases synaptic eN activity. Since both ATP and adenosine function as neuromodulators in the hippocampal networks, influencing its function, profound knowledge of mechanisms by which ectonucleotidases are regulated/modulated is of great importance. © 2019 Elsevier B.V.
T2  - Neuroscience Letters
T1  - Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats
VL  - 712
SP  - 134474
DO  - 10.1016/j.neulet.2019.134474
ER  - 
@article{
author = "Mitrović, Nataša Lj. and Dragić, Milorad and Zarić, Marina and Drakulić, Dunja R. and Nedeljković, Nadežda and Grković, Ivana",
year = "2019",
abstract = "Extracellular adenine nucleotides and nucleosides, such as adenosine-5'-triphosphate (ATP) and adenosine, are among least investigated signaling factors that participate in 17β-estradiol (E2)-mediated synaptic rearrangements in rodent hippocampus. Their levels in the extrasynaptic space are tightly controlled by ecto-nucleoside triphosphate diphosphohydrolases1-3 (NTPDase1-3)/ecto-5'-nucleotidase (eN) enzyme chain. Therefore, the aim of the present study was to get closer insight in the E2-induced decrease in NTPDase and eN activity in the hippocampal synaptic compartment of male rats and to identify estradiol receptors (ERs i.e. ERα, ERβ or GPER1) responsible for the observed effects of E2. In this study we show indiscriminate participation of estradiol receptor α (ERα), -β (ERβ) and G- protein coupled estrogen receptor 1 (GPER1) in the mediation of E2 actions in hippocampal synaptosomes of male rats. Synaptic NTPDase1-3 activities are modulated only through activation of ERβ, while activation of ERα, -β and/or non-classical GPER1 decreases synaptic eN activity. Since both ATP and adenosine function as neuromodulators in the hippocampal networks, influencing its function, profound knowledge of mechanisms by which ectonucleotidases are regulated/modulated is of great importance. © 2019 Elsevier B.V.",
journal = "Neuroscience Letters",
title = "Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats",
volume = "712",
pages = "134474",
doi = "10.1016/j.neulet.2019.134474"
}
Mitrović, N. Lj., Dragić, M., Zarić, M., Drakulić, D. R., Nedeljković, N.,& Grković, I.. (2019). Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats. in Neuroscience Letters, 712, 134474.
https://doi.org/10.1016/j.neulet.2019.134474
Mitrović NL, Dragić M, Zarić M, Drakulić DR, Nedeljković N, Grković I. Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats. in Neuroscience Letters. 2019;712:134474.
doi:10.1016/j.neulet.2019.134474 .
Mitrović, Nataša Lj., Dragić, Milorad, Zarić, Marina, Drakulić, Dunja R., Nedeljković, Nadežda, Grković, Ivana, "Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats" in Neuroscience Letters, 712 (2019):134474,
https://doi.org/10.1016/j.neulet.2019.134474 . .
6
2
6

Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication

Dragić, Milorad; Zarić, Marina; Mitrović, Nataša Lj.; Nedeljković, Nadežda; Grković, Ivana

(2019)

TY  - JOUR
AU  - Dragić, Milorad
AU  - Zarić, Marina
AU  - Mitrović, Nataša Lj.
AU  - Nedeljković, Nadežda
AU  - Grković, Ivana
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8647
AB  - Astrocytes comprise a heterogenic group of glial cells, which perform homeostatic functions in the central nervous system. These cells react to all kind of insults by changing the morphology and function that result in a transition from the quiescent to a reactive phenotype. Trimethyltin (TMT) intoxication, which reproduces pathological events in the hippocampus similar to those associated with seizures and cognitive decline, has been proven as a useful model for studying responses of the glial cells to neurodegeneration. In the present study, we have explored morphological varieties of astrocytes in the hippocampal subregions of ovariectomized female rats exposed to TMT. We have demonstrated an early loss of neurons in CA1 and DG subfields. Distinct morphotypes of protoplasmic astrocytes observed in CA1/CA3 and the hilus of control animals developed different responses to TMT intoxication, as assessed by GFAP-immunohistochemistry. In CA1 subregion, GFAP+ astrocytes preserved their domain organization and responded with typical hypertrophy, while the hilar GFAP+ astrocytes developed atrophy-like phenotype and increased expression of vimentin and nestin 7 days after the exposure. Both reactive and atrophied-like astrocytes expressed Kir4.1 in CA1/CA3 and the hilus of DG, respectively, indicating that these cells did not change their potential for normal activity at this time point of pathology. Together, the results demonstrate the persistence of two protoplasmic morphotypes of astrocytes, with distinct appearance, function, and fate after TMT-induced neurodegeneration, suggesting their pleiotropic roles in the hippocampal response to neurodegeneration. © 2019 IBRO
T2  - Neuroscience
T1  - Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication
VL  - 423
SP  - 38
EP  - 54
DO  - 10.1016/j.neuroscience.2019.10.022
ER  - 
@article{
author = "Dragić, Milorad and Zarić, Marina and Mitrović, Nataša Lj. and Nedeljković, Nadežda and Grković, Ivana",
year = "2019",
abstract = "Astrocytes comprise a heterogenic group of glial cells, which perform homeostatic functions in the central nervous system. These cells react to all kind of insults by changing the morphology and function that result in a transition from the quiescent to a reactive phenotype. Trimethyltin (TMT) intoxication, which reproduces pathological events in the hippocampus similar to those associated with seizures and cognitive decline, has been proven as a useful model for studying responses of the glial cells to neurodegeneration. In the present study, we have explored morphological varieties of astrocytes in the hippocampal subregions of ovariectomized female rats exposed to TMT. We have demonstrated an early loss of neurons in CA1 and DG subfields. Distinct morphotypes of protoplasmic astrocytes observed in CA1/CA3 and the hilus of control animals developed different responses to TMT intoxication, as assessed by GFAP-immunohistochemistry. In CA1 subregion, GFAP+ astrocytes preserved their domain organization and responded with typical hypertrophy, while the hilar GFAP+ astrocytes developed atrophy-like phenotype and increased expression of vimentin and nestin 7 days after the exposure. Both reactive and atrophied-like astrocytes expressed Kir4.1 in CA1/CA3 and the hilus of DG, respectively, indicating that these cells did not change their potential for normal activity at this time point of pathology. Together, the results demonstrate the persistence of two protoplasmic morphotypes of astrocytes, with distinct appearance, function, and fate after TMT-induced neurodegeneration, suggesting their pleiotropic roles in the hippocampal response to neurodegeneration. © 2019 IBRO",
journal = "Neuroscience",
title = "Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication",
volume = "423",
pages = "38-54",
doi = "10.1016/j.neuroscience.2019.10.022"
}
Dragić, M., Zarić, M., Mitrović, N. Lj., Nedeljković, N.,& Grković, I.. (2019). Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication. in Neuroscience, 423, 38-54.
https://doi.org/10.1016/j.neuroscience.2019.10.022
Dragić M, Zarić M, Mitrović NL, Nedeljković N, Grković I. Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication. in Neuroscience. 2019;423:38-54.
doi:10.1016/j.neuroscience.2019.10.022 .
Dragić, Milorad, Zarić, Marina, Mitrović, Nataša Lj., Nedeljković, Nadežda, Grković, Ivana, "Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication" in Neuroscience, 423 (2019):38-54,
https://doi.org/10.1016/j.neuroscience.2019.10.022 . .
2
15
4
12

Prooxidant–antioxidant balance, advanced oxidation protein products and lipid peroxidation in Serbian patients with Parkinson's disease

Miletić, Jadranka; Drakulić, Dunja R.; Pejić, Snežana; Petković, Marijana; Ilić, Tihomir V.; Miljković, Milica; Stefanović, Aleksandra; Prostran, Milica; Stojanov, Marina

(2018)

TY  - JOUR
AU  - Miletić, Jadranka
AU  - Drakulić, Dunja R.
AU  - Pejić, Snežana
AU  - Petković, Marijana
AU  - Ilić, Tihomir V.
AU  - Miljković, Milica
AU  - Stefanović, Aleksandra
AU  - Prostran, Milica
AU  - Stojanov, Marina
PY  - 2018
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7736
AB  - Background: Biomarkers of oxidative stress are relevant in the evaluation of the disease status and prooxidant-antioxidant balance, advanced oxidation protein products and lipid peroxidation products (malondialdehyde and 4-hydroxynonenal) are being extensively evaluated regarding their relationship with clinical presentation and disease severity.Aim of the study: The aim of this study was to evaluate the levels of the above-mentioned parameters in plasma of 39 men and 17 women with Parkinson's disease, originated from the Republic of Serbia and their relation to clinicopathological characteristics (gender, age at examination, duration of the disease, and Hoehn and Yahr score) and oxidative status.Results: The incidence of disease was 2:1 towards males. The investigated oxidative parameters were gender and Hoehn and Yahr related. Significant association of higher Hoehn and Yahr scores was observed for malondialdehyde (p = 0.01) and prooxidant-antioxidant balance (p = 0.02). Relation between oxidant-antioxidant status was further supported by observed positive correlation between 4-hydroxynonenal (p = 0.04) and prooxidant-antioxidant balance (p = 0.03). Finally, the multivariate analysis indicated that prooxidant-antioxidant balance and malondialdehyde were partially determined by gender (10.6% and 7.6%) and Hoehn and Yahr scores (13.6% and 18.8%), while Hoehn and Yahr scores contributed to the variance of advanced oxidation protein products with 13.2%.Conclusion: Our results indicate the higher level of oxidative stress (oxidant-antioxidant imbalance) and possible relation of several markers with gender and disease stage in patients with Parkinson's disease. The analyzed markers could be used to specify the severity of oxidative stress; however, their potential value should be analyzed in further studies.
T2  - International Journal of Neuroscience
T1  - Prooxidant–antioxidant balance, advanced oxidation protein products and lipid peroxidation in Serbian patients with Parkinson's disease
VL  - 128
IS  - 7
SP  - 600
EP  - 607
DO  - 10.1080/00207454.2017.1403916
ER  - 
@article{
author = "Miletić, Jadranka and Drakulić, Dunja R. and Pejić, Snežana and Petković, Marijana and Ilić, Tihomir V. and Miljković, Milica and Stefanović, Aleksandra and Prostran, Milica and Stojanov, Marina",
year = "2018",
abstract = "Background: Biomarkers of oxidative stress are relevant in the evaluation of the disease status and prooxidant-antioxidant balance, advanced oxidation protein products and lipid peroxidation products (malondialdehyde and 4-hydroxynonenal) are being extensively evaluated regarding their relationship with clinical presentation and disease severity.Aim of the study: The aim of this study was to evaluate the levels of the above-mentioned parameters in plasma of 39 men and 17 women with Parkinson's disease, originated from the Republic of Serbia and their relation to clinicopathological characteristics (gender, age at examination, duration of the disease, and Hoehn and Yahr score) and oxidative status.Results: The incidence of disease was 2:1 towards males. The investigated oxidative parameters were gender and Hoehn and Yahr related. Significant association of higher Hoehn and Yahr scores was observed for malondialdehyde (p = 0.01) and prooxidant-antioxidant balance (p = 0.02). Relation between oxidant-antioxidant status was further supported by observed positive correlation between 4-hydroxynonenal (p = 0.04) and prooxidant-antioxidant balance (p = 0.03). Finally, the multivariate analysis indicated that prooxidant-antioxidant balance and malondialdehyde were partially determined by gender (10.6% and 7.6%) and Hoehn and Yahr scores (13.6% and 18.8%), while Hoehn and Yahr scores contributed to the variance of advanced oxidation protein products with 13.2%.Conclusion: Our results indicate the higher level of oxidative stress (oxidant-antioxidant imbalance) and possible relation of several markers with gender and disease stage in patients with Parkinson's disease. The analyzed markers could be used to specify the severity of oxidative stress; however, their potential value should be analyzed in further studies.",
journal = "International Journal of Neuroscience",
title = "Prooxidant–antioxidant balance, advanced oxidation protein products and lipid peroxidation in Serbian patients with Parkinson's disease",
volume = "128",
number = "7",
pages = "600-607",
doi = "10.1080/00207454.2017.1403916"
}
Miletić, J., Drakulić, D. R., Pejić, S., Petković, M., Ilić, T. V., Miljković, M., Stefanović, A., Prostran, M.,& Stojanov, M.. (2018). Prooxidant–antioxidant balance, advanced oxidation protein products and lipid peroxidation in Serbian patients with Parkinson's disease. in International Journal of Neuroscience, 128(7), 600-607.
https://doi.org/10.1080/00207454.2017.1403916
Miletić J, Drakulić DR, Pejić S, Petković M, Ilić TV, Miljković M, Stefanović A, Prostran M, Stojanov M. Prooxidant–antioxidant balance, advanced oxidation protein products and lipid peroxidation in Serbian patients with Parkinson's disease. in International Journal of Neuroscience. 2018;128(7):600-607.
doi:10.1080/00207454.2017.1403916 .
Miletić, Jadranka, Drakulić, Dunja R., Pejić, Snežana, Petković, Marijana, Ilić, Tihomir V., Miljković, Milica, Stefanović, Aleksandra, Prostran, Milica, Stojanov, Marina, "Prooxidant–antioxidant balance, advanced oxidation protein products and lipid peroxidation in Serbian patients with Parkinson's disease" in International Journal of Neuroscience, 128, no. 7 (2018):600-607,
https://doi.org/10.1080/00207454.2017.1403916 . .
20
11
16

Regional-specific effects of cerebral ischemia/reperfusion and dehydroepiandrosterone on synaptic NMDAR/PSD-95 complex in male Wistar rats

Zarić, Marina; Drakulić, Dunja R.; Guševac Stojanović, Ivana; Mitrović, Nataša Lj.; Grković, Ivana; Martinović, Jelena

(2018)

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 . .
11
6
11

17 beta-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes

Mitrović, Nataša Lj.; Zarić, Marina; Drakulić, Dunja R.; Martinović, Jelena; Sevigny, Jean; Stanojlović, Miloš R.; Nedeljković, Nadežda; Grković, Ivana

(2017)

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 . .
13
11
13

Plasma phospholipid changes are associated with response to chemotherapy in non-Hodgkin lymphoma patients

Cvetković, Zorica; Milošević, Maja; Cvetković, Bora; Masnikosa, Romana; Arsić, Aleksandra; Petrović, Snježana; Vučić, Vesna

(2017)

TY  - JOUR
AU  - Cvetković, Zorica
AU  - Milošević, Maja
AU  - Cvetković, Bora
AU  - Masnikosa, Romana
AU  - Arsić, Aleksandra
AU  - Petrović, Snježana
AU  - Vučić, Vesna
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1489
AB  - Limited studies have been performed to associate abnormal phospholipid (PL) profile and disease activity in hematological malignancies, including non-Hodgkin lymphoma (NHL). The aim of his study was to evaluate the levels of plasma PL fractions in NHL patients, in response to chemotherapy. Forty non-treated patients with NHL and 25 healthy individuals were recruited. Blood samples from patients were taken before chemotherapy, after 3 cycles and after the end of the treatment, and PL fractions were resolved by one-dimensional thin-layer chromatography. To assess potential relationship between plasma PL profile and response to therapy, patients were divided according to clinical outcome in 3 groups: complete remission (CR), stable disease (SD) and progression (PG). Despite significant differences between NHL patients and healthy controls, no differences were found at baseline among patients divided according to clinical outcome. During and after chemotherapy important alterations in PL profile were observed. Levels of total PLs and all PL fractions decreased in patients with PG while in patients who responded to therapy (CR, SD) PLs significantly increased. Results of our study suggest that changes of total PLs and PL fractions during the therapy are associated with the effects of therapy and clinical outcome in patients with NHL. (C) 2017 Elsevier Ltd. All rights reserved.
T2  - Leukemia Research
T1  - Plasma phospholipid changes are associated with response to chemotherapy in non-Hodgkin lymphoma patients
VL  - 54
SP  - 39
EP  - 46
DO  - 10.1016/j.leukres.2017.01.004
ER  - 
@article{
author = "Cvetković, Zorica and Milošević, Maja and Cvetković, Bora and Masnikosa, Romana and Arsić, Aleksandra and Petrović, Snježana and Vučić, Vesna",
year = "2017",
abstract = "Limited studies have been performed to associate abnormal phospholipid (PL) profile and disease activity in hematological malignancies, including non-Hodgkin lymphoma (NHL). The aim of his study was to evaluate the levels of plasma PL fractions in NHL patients, in response to chemotherapy. Forty non-treated patients with NHL and 25 healthy individuals were recruited. Blood samples from patients were taken before chemotherapy, after 3 cycles and after the end of the treatment, and PL fractions were resolved by one-dimensional thin-layer chromatography. To assess potential relationship between plasma PL profile and response to therapy, patients were divided according to clinical outcome in 3 groups: complete remission (CR), stable disease (SD) and progression (PG). Despite significant differences between NHL patients and healthy controls, no differences were found at baseline among patients divided according to clinical outcome. During and after chemotherapy important alterations in PL profile were observed. Levels of total PLs and all PL fractions decreased in patients with PG while in patients who responded to therapy (CR, SD) PLs significantly increased. Results of our study suggest that changes of total PLs and PL fractions during the therapy are associated with the effects of therapy and clinical outcome in patients with NHL. (C) 2017 Elsevier Ltd. All rights reserved.",
journal = "Leukemia Research",
title = "Plasma phospholipid changes are associated with response to chemotherapy in non-Hodgkin lymphoma patients",
volume = "54",
pages = "39-46",
doi = "10.1016/j.leukres.2017.01.004"
}
Cvetković, Z., Milošević, M., Cvetković, B., Masnikosa, R., Arsić, A., Petrović, S.,& Vučić, V.. (2017). Plasma phospholipid changes are associated with response to chemotherapy in non-Hodgkin lymphoma patients. in Leukemia Research, 54, 39-46.
https://doi.org/10.1016/j.leukres.2017.01.004
Cvetković Z, Milošević M, Cvetković B, Masnikosa R, Arsić A, Petrović S, Vučić V. Plasma phospholipid changes are associated with response to chemotherapy in non-Hodgkin lymphoma patients. in Leukemia Research. 2017;54:39-46.
doi:10.1016/j.leukres.2017.01.004 .
Cvetković, Zorica, Milošević, Maja, Cvetković, Bora, Masnikosa, Romana, Arsić, Aleksandra, Petrović, Snježana, Vučić, Vesna, "Plasma phospholipid changes are associated with response to chemotherapy in non-Hodgkin lymphoma patients" in Leukemia Research, 54 (2017):39-46,
https://doi.org/10.1016/j.leukres.2017.01.004 . .
5
4
4

Expression of ecto-nucleoside triphosphate diphosphohydrolase3 (NTPDase3) in the female rat brain during postnatal development

Grković, Ivana; Bjelobaba, Ivana; Mitrović, Nataša Lj.; Lavrnja, Irena; Drakulić, Dunja R.; Martinović, Jelena; Stanojlović, Miloš R.; Horvat, Anica; Nedeljković, Nadežda

(2016)

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 . .
1
8
5
8

17 beta-ESTRADIOL UPREGULATES ECTO-5 -NUCLEOTIDASE (CD73) IN HIPPOCAMPAL SYNAPTOSOMES OF FEMALE RATS THROUGH ACTION MEDIATED BY ESTROGEN RECEPTOR-alpha AND -beta

Mitrović, Nataša Lj.; Zarić, Marina; Drakulić, Dunja R.; Martinović, Jelena; Stanojlović, Miloš R.; Sevigny, Jean; Horvat, Anica; Nedeljković, Nadežda; Grković, Ivana

(Elsevier, 2016)

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 . .
14
10
14

Repeated Estradiol Treatment Attenuates Chronic Cerebral Hypoperfusion-Induced Neurodegeneration in Rat Hippocampus

Stanojlović, Miloš R.; Guševac, Ivana; Grković, Ivana; Mitrović, Nataša Lj.; Martinović, Jelena; Horvat, Anica; Drakulić, Dunja R.

(2016)

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 . .
2
11
7
8

Regional and sex-related differences in modulating effects of female sex steroids on ecto-5-nucleotidase expression in the rat cerebral cortex and hippocampus

Mitrović, Nataša Lj.; Guševac, Ivana; Drakulić, Dunja R.; Stanojlović, Miloš R.; Martinović, Jelena; Sevigny, Jean; Horvat, Anica; Nedeljković, Nadežda; Grković, Ivana

(2016)

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 . .
12
8
12

Brain Injury Alters Ectonucleotidase Activities and Adenine Nucleotide Levels in Rat Serum

Laketa, Danijela; Savić, Jasmina; Bjelobaba, Ivana; Lavrnja, Irene; Vasić, Vesna M.; Stojiljković, Mirjana; Nedeljković, Nadežda

(2015)

TY  - JOUR
AU  - Laketa, Danijela
AU  - Savić, Jasmina
AU  - Bjelobaba, Ivana
AU  - Lavrnja, Irene
AU  - Vasić, Vesna M.
AU  - Stojiljković, Mirjana
AU  - Nedeljković, Nadežda
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/385
AB  - Background: Cortical stab injury (CSI) induces changes in the activity, expression and cellular distribution of specific ectonucleotidases at the injury site. Also, several experimentally induced neuropathologies are associated with changes in soluble ectonucleotidase activities in the plasma and serum, whilst various insults to the brain alter purine compounds levels in cerebrospinal fluid, but also in serum, indicating that insults to the brain may induce alterations in nucleotides release and rate of their hydrolysis in the vascular system. Since adenine nucleotides and adenosine regulate diverse cellular functions in the vascular system, including vascular tone, platelet aggregation and inflammatory responses of lymphocytes and macrophages, alterations of ectonucleotidase activities in the vascular system may be relevant for the clinical outcome of the primary insult. Methods: We explored ectonucleotidase activities using specific enzyme assays and determined adenine nucleotides concentrations by the UPLC method in the rat serum after cortical stab injury. Results: At 4-h post-injury, ATP and AMP hydrolysis increased by about 60% and 40%, respectively, while phosphodiesterase activity remained unchanged. Also, at 4-h postinjury a marked decrease in ATP concentration and more than 2-fold increase in AMP concentration were recorded. Conclusions: CSI induces rapid up-regulation of nucleotide catabolizing soluble ectonucleotidases in rat serum, which leads to the observed shift in serum nucleotide levels. The results obtained imply that ectonucleotidases and adenine nucleotides participate in the communication between the brain and the vascular system in physiological and pathological conditions and thereby may be involved in the development of various human neuropathologies.
T2  - Journal of Medical Biochemistry
T1  - Brain Injury Alters Ectonucleotidase Activities and Adenine Nucleotide Levels in Rat Serum
VL  - 34
IS  - 2
SP  - 215
EP  - 222
DO  - 10.2478/jomb-2014-0025
ER  - 
@article{
author = "Laketa, Danijela and Savić, Jasmina and Bjelobaba, Ivana and Lavrnja, Irene and Vasić, Vesna M. and Stojiljković, Mirjana and Nedeljković, Nadežda",
year = "2015",
abstract = "Background: Cortical stab injury (CSI) induces changes in the activity, expression and cellular distribution of specific ectonucleotidases at the injury site. Also, several experimentally induced neuropathologies are associated with changes in soluble ectonucleotidase activities in the plasma and serum, whilst various insults to the brain alter purine compounds levels in cerebrospinal fluid, but also in serum, indicating that insults to the brain may induce alterations in nucleotides release and rate of their hydrolysis in the vascular system. Since adenine nucleotides and adenosine regulate diverse cellular functions in the vascular system, including vascular tone, platelet aggregation and inflammatory responses of lymphocytes and macrophages, alterations of ectonucleotidase activities in the vascular system may be relevant for the clinical outcome of the primary insult. Methods: We explored ectonucleotidase activities using specific enzyme assays and determined adenine nucleotides concentrations by the UPLC method in the rat serum after cortical stab injury. Results: At 4-h post-injury, ATP and AMP hydrolysis increased by about 60% and 40%, respectively, while phosphodiesterase activity remained unchanged. Also, at 4-h postinjury a marked decrease in ATP concentration and more than 2-fold increase in AMP concentration were recorded. Conclusions: CSI induces rapid up-regulation of nucleotide catabolizing soluble ectonucleotidases in rat serum, which leads to the observed shift in serum nucleotide levels. The results obtained imply that ectonucleotidases and adenine nucleotides participate in the communication between the brain and the vascular system in physiological and pathological conditions and thereby may be involved in the development of various human neuropathologies.",
journal = "Journal of Medical Biochemistry",
title = "Brain Injury Alters Ectonucleotidase Activities and Adenine Nucleotide Levels in Rat Serum",
volume = "34",
number = "2",
pages = "215-222",
doi = "10.2478/jomb-2014-0025"
}
Laketa, D., Savić, J., Bjelobaba, I., Lavrnja, I., Vasić, V. M., Stojiljković, M.,& Nedeljković, N.. (2015). Brain Injury Alters Ectonucleotidase Activities and Adenine Nucleotide Levels in Rat Serum. in Journal of Medical Biochemistry, 34(2), 215-222.
https://doi.org/10.2478/jomb-2014-0025
Laketa D, Savić J, Bjelobaba I, Lavrnja I, Vasić VM, Stojiljković M, Nedeljković N. Brain Injury Alters Ectonucleotidase Activities and Adenine Nucleotide Levels in Rat Serum. in Journal of Medical Biochemistry. 2015;34(2):215-222.
doi:10.2478/jomb-2014-0025 .
Laketa, Danijela, Savić, Jasmina, Bjelobaba, Ivana, Lavrnja, Irene, Vasić, Vesna M., Stojiljković, Mirjana, Nedeljković, Nadežda, "Brain Injury Alters Ectonucleotidase Activities and Adenine Nucleotide Levels in Rat Serum" in Journal of Medical Biochemistry, 34, no. 2 (2015):215-222,
https://doi.org/10.2478/jomb-2014-0025 . .
12
10
11

Upregulation of Nucleoside Triphosphate Diphosphohydrolase-1 and Ecto-5-Nucleotidase in Rat Hippocampus after Repeated Low-Dose Dexamethasone Administration

Drakulić, Dunja R.; Stanojlović, Miloš R.; Nedeljković, Nadežda; Grković, Ivana; Velickovic, Natasa; Guševac, Ivana; Mitrović, Nataša Lj.; Buzadzic, Ivana; Horvat, Anica

(2015)

TY  - JOUR
AU  - Drakulić, Dunja R.
AU  - Stanojlović, Miloš R.
AU  - Nedeljković, Nadežda
AU  - Grković, Ivana
AU  - Velickovic, Natasa
AU  - Guševac, Ivana
AU  - Mitrović, Nataša Lj.
AU  - Buzadzic, Ivana
AU  - Horvat, Anica
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/446
AB  - Although dexamethasone (DEX), a synthetic glucocorticoid receptor (GR) analog with profound effects on energy metabolism, immune system, and hypothalamic-pituitary-adrenal axis, is widely used therapeutically, its impact on the brain is poorly understood. The aim of the present study was to explore the effect of repeated low-dose DEX administration on the activity and expression of the ectonucleotidase enzymes which hydrolyze and therefore control extracellular ATP and adenosine concentrations in the synaptic cleft. Ectonucleotidases tested were ectonucleoside triphosphate diphosphohydrolase 1-3 (NTPDase1-3) and ecto-5-nucleotidase (eN), whereas the effects were evaluated in two brain areas that show different sensitivity to glucocorticoid action, hippocampus, and cerebral cortex. In the hippocampus, but not in cerebral cortex, modest level of neurodegenerative changes as well as increase in ATP, ADP, and AMP hydrolysis and upregulation of NTPDase1 and eN mRNA expression ensued under the influence of DEX. The observed pattern of ectonucleotidase activation, which creates tissue volume with enhanced capacity for adenosine formation, is the hallmark of the response after different insults to the brain.
T2  - Journal of Molecular Neuroscience
T1  - Upregulation of Nucleoside Triphosphate Diphosphohydrolase-1 and Ecto-5-Nucleotidase in Rat Hippocampus after Repeated Low-Dose Dexamethasone Administration
VL  - 55
IS  - 4
SP  - 959
EP  - 967
DO  - 10.1007/s12031-014-0452-y
ER  - 
@article{
author = "Drakulić, Dunja R. and Stanojlović, Miloš R. and Nedeljković, Nadežda and Grković, Ivana and Velickovic, Natasa and Guševac, Ivana and Mitrović, Nataša Lj. and Buzadzic, Ivana and Horvat, Anica",
year = "2015",
abstract = "Although dexamethasone (DEX), a synthetic glucocorticoid receptor (GR) analog with profound effects on energy metabolism, immune system, and hypothalamic-pituitary-adrenal axis, is widely used therapeutically, its impact on the brain is poorly understood. The aim of the present study was to explore the effect of repeated low-dose DEX administration on the activity and expression of the ectonucleotidase enzymes which hydrolyze and therefore control extracellular ATP and adenosine concentrations in the synaptic cleft. Ectonucleotidases tested were ectonucleoside triphosphate diphosphohydrolase 1-3 (NTPDase1-3) and ecto-5-nucleotidase (eN), whereas the effects were evaluated in two brain areas that show different sensitivity to glucocorticoid action, hippocampus, and cerebral cortex. In the hippocampus, but not in cerebral cortex, modest level of neurodegenerative changes as well as increase in ATP, ADP, and AMP hydrolysis and upregulation of NTPDase1 and eN mRNA expression ensued under the influence of DEX. The observed pattern of ectonucleotidase activation, which creates tissue volume with enhanced capacity for adenosine formation, is the hallmark of the response after different insults to the brain.",
journal = "Journal of Molecular Neuroscience",
title = "Upregulation of Nucleoside Triphosphate Diphosphohydrolase-1 and Ecto-5-Nucleotidase in Rat Hippocampus after Repeated Low-Dose Dexamethasone Administration",
volume = "55",
number = "4",
pages = "959-967",
doi = "10.1007/s12031-014-0452-y"
}
Drakulić, D. R., Stanojlović, M. R., Nedeljković, N., Grković, I., Velickovic, N., Guševac, I., Mitrović, N. Lj., Buzadzic, I.,& Horvat, A.. (2015). Upregulation of Nucleoside Triphosphate Diphosphohydrolase-1 and Ecto-5-Nucleotidase in Rat Hippocampus after Repeated Low-Dose Dexamethasone Administration. in Journal of Molecular Neuroscience, 55(4), 959-967.
https://doi.org/10.1007/s12031-014-0452-y
Drakulić DR, Stanojlović MR, Nedeljković N, Grković I, Velickovic N, Guševac I, Mitrović NL, Buzadzic I, Horvat A. Upregulation of Nucleoside Triphosphate Diphosphohydrolase-1 and Ecto-5-Nucleotidase in Rat Hippocampus after Repeated Low-Dose Dexamethasone Administration. in Journal of Molecular Neuroscience. 2015;55(4):959-967.
doi:10.1007/s12031-014-0452-y .
Drakulić, Dunja R., Stanojlović, Miloš R., Nedeljković, Nadežda, Grković, Ivana, Velickovic, Natasa, Guševac, Ivana, Mitrović, Nataša Lj., Buzadzic, Ivana, Horvat, Anica, "Upregulation of Nucleoside Triphosphate Diphosphohydrolase-1 and Ecto-5-Nucleotidase in Rat Hippocampus after Repeated Low-Dose Dexamethasone Administration" in Journal of Molecular Neuroscience, 55, no. 4 (2015):959-967,
https://doi.org/10.1007/s12031-014-0452-y . .
6
3
5

Repeated low-dose 17 beta-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia

Stanojlović, Miloš R.; Martinović, Jelena; Guševac, Ivana; Grković, Ivana; Mitrović, Nataša Lj.; Zarić, Marina; Horvat, Anica; Drakulić, Dunja R.

(2015)

TY  - JOUR
AU  - Stanojlović, Miloš R.
AU  - Martinović, Jelena
AU  - Guševac, Ivana
AU  - Grković, Ivana
AU  - Mitrović, Nataša Lj.
AU  - Zarić, Marina
AU  - Horvat, Anica
AU  - Drakulić, Dunja R.
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/527
AB  - Disturbance in blood circulation is associated with numerous pathological conditions characterized by cognitive decline and neurodegeneration. Activation of pro-apoptotic signaling previously detected in the synaptosomal fraction may underlie neurodegeneration in the prefrontal cortex of rats submitted to permanent bilateral common carotid arteries occlusion (two-vessel occlusion, 2VO). 17 beta-Estradiol (E) exerts potent neuroprotective effects in the brain affecting, among other, ischemia-induced pathological changes. As most significant changes in rats submitted to 2VO were observed on 7th day following the insult, of interest was to examine whether 7 day treatment with low dose of E (33.3 mu g/kg/day) prevents formerly reported neurodegeneration and may represent additional therapy during the early post-ischemic period. Role of E treatment on apoptotic pathway was monitored on Bcl-2 family members, cytochrome c, caspase 3 and PARP protein level in the synaptosomal (P2) fraction of the prefrontal cortex. Furthermore, changes of these proteins were examined in the cytosolic, mitochondrial and nuclear fraction, with the emphasis on potential involvement of extracellular signal-regulated kinases (ERK) and protein kinase B (Akt) activation and their role in nuclear translocation of transcriptional nuclear factor kappa B (NF-kB) associated with alteration of Box and Bcl-2 gene expression. The extent of cellular damage was determined using DNA fragmentation and Fluoro-Jade B staining. The absence of activation of apoptotic cascade both in the P2 and cell accompanied with decreased DNA fragmentation and number of degenerating neurons clearly indicates that E treatment ensures the efficient protection against ischemic insult. Moreover, E-mediated modulation of pro-apoptotic signaling in the cortical cellular fractions involves cooperative activation of ERK and Akt, which may be implicated in the observed prevention of neurodegenerative changes. (C) 2015 Elsevier Ltd. All rights reserved.
T2  - Neurochemistry International
T1  - Repeated low-dose 17 beta-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia
VL  - 83-84
SP  - 1
EP  - 8
DO  - 10.1016/j.neuint.2015.03.002
ER  - 
@article{
author = "Stanojlović, Miloš R. and Martinović, Jelena and Guševac, Ivana and Grković, Ivana and Mitrović, Nataša Lj. and Zarić, Marina and Horvat, Anica and Drakulić, Dunja R.",
year = "2015",
abstract = "Disturbance in blood circulation is associated with numerous pathological conditions characterized by cognitive decline and neurodegeneration. Activation of pro-apoptotic signaling previously detected in the synaptosomal fraction may underlie neurodegeneration in the prefrontal cortex of rats submitted to permanent bilateral common carotid arteries occlusion (two-vessel occlusion, 2VO). 17 beta-Estradiol (E) exerts potent neuroprotective effects in the brain affecting, among other, ischemia-induced pathological changes. As most significant changes in rats submitted to 2VO were observed on 7th day following the insult, of interest was to examine whether 7 day treatment with low dose of E (33.3 mu g/kg/day) prevents formerly reported neurodegeneration and may represent additional therapy during the early post-ischemic period. Role of E treatment on apoptotic pathway was monitored on Bcl-2 family members, cytochrome c, caspase 3 and PARP protein level in the synaptosomal (P2) fraction of the prefrontal cortex. Furthermore, changes of these proteins were examined in the cytosolic, mitochondrial and nuclear fraction, with the emphasis on potential involvement of extracellular signal-regulated kinases (ERK) and protein kinase B (Akt) activation and their role in nuclear translocation of transcriptional nuclear factor kappa B (NF-kB) associated with alteration of Box and Bcl-2 gene expression. The extent of cellular damage was determined using DNA fragmentation and Fluoro-Jade B staining. The absence of activation of apoptotic cascade both in the P2 and cell accompanied with decreased DNA fragmentation and number of degenerating neurons clearly indicates that E treatment ensures the efficient protection against ischemic insult. Moreover, E-mediated modulation of pro-apoptotic signaling in the cortical cellular fractions involves cooperative activation of ERK and Akt, which may be implicated in the observed prevention of neurodegenerative changes. (C) 2015 Elsevier Ltd. All rights reserved.",
journal = "Neurochemistry International",
title = "Repeated low-dose 17 beta-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia",
volume = "83-84",
pages = "1-8",
doi = "10.1016/j.neuint.2015.03.002"
}
Stanojlović, M. R., Martinović, J., Guševac, I., Grković, I., Mitrović, N. Lj., Zarić, M., Horvat, A.,& Drakulić, D. R.. (2015). Repeated low-dose 17 beta-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia. in Neurochemistry International, 83-84, 1-8.
https://doi.org/10.1016/j.neuint.2015.03.002
Stanojlović MR, Martinović J, Guševac I, Grković I, Mitrović NL, Zarić M, Horvat A, Drakulić DR. Repeated low-dose 17 beta-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia. in Neurochemistry International. 2015;83-84:1-8.
doi:10.1016/j.neuint.2015.03.002 .
Stanojlović, Miloš R., Martinović, Jelena, Guševac, Ivana, Grković, Ivana, Mitrović, Nataša Lj., Zarić, Marina, Horvat, Anica, Drakulić, Dunja R., "Repeated low-dose 17 beta-estradiol treatment prevents activation of apoptotic signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex following cerebral ischemia" in Neurochemistry International, 83-84 (2015):1-8,
https://doi.org/10.1016/j.neuint.2015.03.002 . .
1
13
11
13

Effects of Chronic Cerebral Hypoperfusion and Low-Dose Progesterone Treatment on Apoptotic Processes, Expression and Subcellular Localization of Key Elements Within Akt and Erk Signaling Pathways in Rat Hippocampus

Stanojlović, Miloš R.; Guševac, Ivana; Grković, Ivana; Martinović, Jelena; Mitrović, Nataša Lj.; Zarić, Marina; Horvat, Anica; Drakulić, Dunja R.

(Elsevier, 2015)

TY  - JOUR
AU  - Stanojlović, Miloš R.
AU  - Guševac, Ivana
AU  - Grković, Ivana
AU  - Martinović, Jelena
AU  - Mitrović, Nataša Lj.
AU  - Zarić, Marina
AU  - Horvat, Anica
AU  - Drakulić, Dunja R.
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/846
AB  - The present study attempted to investigate how chronic cerebral hypoperfusion (CCH) and repeated low-dose progesterone (P) treatment affect gene and protein expression, subcellular distribution of key apoptotic elements within protein kinase B (Akt) and extracellular signal-regulated kinases (Erk) signal transduction pathways, as well as neurodegenerative processes and behavior. The results revealed the absence of Erk activation in CCH in cytosolic and synaptosomal fractions, indicating a lower threshold of Akt activation in brain ischemia, while P increased their levels above control values. CCH induced an increase in caspase 3 (Casp 3) and poly (ADP-ribose) polymerase (PARP) gene and protein expression. However, P restored expression of examined molecules in all observed fractions, except for the levels of Casp 3 in synapses which highlighted its possible non-apoptotic or even protective function. Our study showed the absence of nuclear factor kappa-light-chain-enhancer of activated b cells (NF-kappa B) response to this type of ischemic condition and its strong activation under the influence of P. Further, the initial increase in the number of apoptotic cells and amount of DNA fragmentation induced by CCH was significantly reduced by P. Finally, P reversed the CCH-induced reduction in locomotor activity, while promoting a substantial decrease in anxiety-related behavior. Our findings support the concept that repeated low-dose post-ischemic P treatment reduces CCH-induced neurodegeneration in the hippocampus. Neuroprotection is initiated through the activation of investigated kinases and regulation of their downstream molecules in subcellular specific manner, indicating that this treatment may be a promising therapy for alleviation of CCH-induced pathologies. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
PB  - Elsevier
T2  - Neuroscience
T1  - Effects of Chronic Cerebral Hypoperfusion and Low-Dose Progesterone Treatment on Apoptotic Processes, Expression and Subcellular Localization of Key Elements Within Akt and Erk Signaling Pathways in Rat Hippocampus
VL  - 311
SP  - 308
EP  - 321
DO  - 10.1016/j.neuroscience.2015.10.040
ER  - 
@article{
author = "Stanojlović, Miloš R. and Guševac, Ivana and Grković, Ivana and Martinović, Jelena and Mitrović, Nataša Lj. and Zarić, Marina and Horvat, Anica and Drakulić, Dunja R.",
year = "2015",
abstract = "The present study attempted to investigate how chronic cerebral hypoperfusion (CCH) and repeated low-dose progesterone (P) treatment affect gene and protein expression, subcellular distribution of key apoptotic elements within protein kinase B (Akt) and extracellular signal-regulated kinases (Erk) signal transduction pathways, as well as neurodegenerative processes and behavior. The results revealed the absence of Erk activation in CCH in cytosolic and synaptosomal fractions, indicating a lower threshold of Akt activation in brain ischemia, while P increased their levels above control values. CCH induced an increase in caspase 3 (Casp 3) and poly (ADP-ribose) polymerase (PARP) gene and protein expression. However, P restored expression of examined molecules in all observed fractions, except for the levels of Casp 3 in synapses which highlighted its possible non-apoptotic or even protective function. Our study showed the absence of nuclear factor kappa-light-chain-enhancer of activated b cells (NF-kappa B) response to this type of ischemic condition and its strong activation under the influence of P. Further, the initial increase in the number of apoptotic cells and amount of DNA fragmentation induced by CCH was significantly reduced by P. Finally, P reversed the CCH-induced reduction in locomotor activity, while promoting a substantial decrease in anxiety-related behavior. Our findings support the concept that repeated low-dose post-ischemic P treatment reduces CCH-induced neurodegeneration in the hippocampus. Neuroprotection is initiated through the activation of investigated kinases and regulation of their downstream molecules in subcellular specific manner, indicating that this treatment may be a promising therapy for alleviation of CCH-induced pathologies. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.",
publisher = "Elsevier",
journal = "Neuroscience",
title = "Effects of Chronic Cerebral Hypoperfusion and Low-Dose Progesterone Treatment on Apoptotic Processes, Expression and Subcellular Localization of Key Elements Within Akt and Erk Signaling Pathways in Rat Hippocampus",
volume = "311",
pages = "308-321",
doi = "10.1016/j.neuroscience.2015.10.040"
}
Stanojlović, M. R., Guševac, I., Grković, I., Martinović, J., Mitrović, N. Lj., Zarić, M., Horvat, A.,& Drakulić, D. R.. (2015). Effects of Chronic Cerebral Hypoperfusion and Low-Dose Progesterone Treatment on Apoptotic Processes, Expression and Subcellular Localization of Key Elements Within Akt and Erk Signaling Pathways in Rat Hippocampus. in Neuroscience
Elsevier., 311, 308-321.
https://doi.org/10.1016/j.neuroscience.2015.10.040
Stanojlović MR, Guševac I, Grković I, Martinović J, Mitrović NL, Zarić M, Horvat A, Drakulić DR. Effects of Chronic Cerebral Hypoperfusion and Low-Dose Progesterone Treatment on Apoptotic Processes, Expression and Subcellular Localization of Key Elements Within Akt and Erk Signaling Pathways in Rat Hippocampus. in Neuroscience. 2015;311:308-321.
doi:10.1016/j.neuroscience.2015.10.040 .
Stanojlović, Miloš R., Guševac, Ivana, Grković, Ivana, Martinović, Jelena, Mitrović, Nataša Lj., Zarić, Marina, Horvat, Anica, Drakulić, Dunja R., "Effects of Chronic Cerebral Hypoperfusion and Low-Dose Progesterone Treatment on Apoptotic Processes, Expression and Subcellular Localization of Key Elements Within Akt and Erk Signaling Pathways in Rat Hippocampus" in Neuroscience, 311 (2015):308-321,
https://doi.org/10.1016/j.neuroscience.2015.10.040 . .
10
12
9
11

Time Course of Cerebral Hypoperfusion-Induced Neurodegenerative Changes in the Cortex of Male and Female Rats

Stanojlović, Miloš R.; Horvat, Anica; Guševac, Ivana; Grković, Ivana; Mitrović, Nataša Lj.; Buzadzic, I.; Drakulić, Dunja R.

(2014)

TY  - JOUR
AU  - Stanojlović, Miloš R.
AU  - Horvat, Anica
AU  - Guševac, Ivana
AU  - Grković, Ivana
AU  - Mitrović, Nataša Lj.
AU  - Buzadzic, I.
AU  - Drakulić, Dunja R.
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5445
AB  - To study time-dependent and gender-specific intracellular and biochemical mechanisms that lead to neurodegeneration due to moderate but persistent reduction of cerebral blood flow, adult male and female Wistar rats were divided into two main groups controls that underwent sham operation and animals subjected to permanent bilateral occlusion of common carotid arteries. Animals were sacrificed 3, 7 or 90 days following the insult. Expression of several apoptotic proteins in synaptic fractions along with Fluoro-Jade B staining and DNA fragmentation assay were used to estimate the apoptotic processes and potential neurodegeneration in cerebral cortex. Data suggest a time-specific increase of Bax as well as time- and gender-associated down-regulation in protein expression of Bcl-2, up-regulation of procaspase 3, accompanied with increased cleavage of procaspase 3 and PARP in synaptic terminals. Furthermore, time- but not gender-specific neurodegeneration was observed. Our findings support the concept of time- and gender-associated response to permanent bilateral occlusion of common carotid arteries, which would enable better understanding of the mechanisms underlying cerebral hypoperfusion.
T2  - Folia Biologica
T1  - Time Course of Cerebral Hypoperfusion-Induced Neurodegenerative Changes in the Cortex of Male and Female Rats
VL  - 60
IS  - 3
SP  - 123
EP  - 132
UR  - https://hdl.handle.net/21.15107/rcub_vinar_5445
ER  - 
@article{
author = "Stanojlović, Miloš R. and Horvat, Anica and Guševac, Ivana and Grković, Ivana and Mitrović, Nataša Lj. and Buzadzic, I. and Drakulić, Dunja R.",
year = "2014",
abstract = "To study time-dependent and gender-specific intracellular and biochemical mechanisms that lead to neurodegeneration due to moderate but persistent reduction of cerebral blood flow, adult male and female Wistar rats were divided into two main groups controls that underwent sham operation and animals subjected to permanent bilateral occlusion of common carotid arteries. Animals were sacrificed 3, 7 or 90 days following the insult. Expression of several apoptotic proteins in synaptic fractions along with Fluoro-Jade B staining and DNA fragmentation assay were used to estimate the apoptotic processes and potential neurodegeneration in cerebral cortex. Data suggest a time-specific increase of Bax as well as time- and gender-associated down-regulation in protein expression of Bcl-2, up-regulation of procaspase 3, accompanied with increased cleavage of procaspase 3 and PARP in synaptic terminals. Furthermore, time- but not gender-specific neurodegeneration was observed. Our findings support the concept of time- and gender-associated response to permanent bilateral occlusion of common carotid arteries, which would enable better understanding of the mechanisms underlying cerebral hypoperfusion.",
journal = "Folia Biologica",
title = "Time Course of Cerebral Hypoperfusion-Induced Neurodegenerative Changes in the Cortex of Male and Female Rats",
volume = "60",
number = "3",
pages = "123-132",
url = "https://hdl.handle.net/21.15107/rcub_vinar_5445"
}
Stanojlović, M. R., Horvat, A., Guševac, I., Grković, I., Mitrović, N. Lj., Buzadzic, I.,& Drakulić, D. R.. (2014). Time Course of Cerebral Hypoperfusion-Induced Neurodegenerative Changes in the Cortex of Male and Female Rats. in Folia Biologica, 60(3), 123-132.
https://hdl.handle.net/21.15107/rcub_vinar_5445
Stanojlović MR, Horvat A, Guševac I, Grković I, Mitrović NL, Buzadzic I, Drakulić DR. Time Course of Cerebral Hypoperfusion-Induced Neurodegenerative Changes in the Cortex of Male and Female Rats. in Folia Biologica. 2014;60(3):123-132.
https://hdl.handle.net/21.15107/rcub_vinar_5445 .
Stanojlović, Miloš R., Horvat, Anica, Guševac, Ivana, Grković, Ivana, Mitrović, Nataša Lj., Buzadzic, I., Drakulić, Dunja R., "Time Course of Cerebral Hypoperfusion-Induced Neurodegenerative Changes in the Cortex of Male and Female Rats" in Folia Biologica, 60, no. 3 (2014):123-132,
https://hdl.handle.net/21.15107/rcub_vinar_5445 .
6

Efekat estradiola u modulaciji apoptotskih signala u moždanoj kori i hipokampusu pacova tokom hronične moždane hipoperfuzije

Stanojlović, Miloš R.

(Универзитет у Београду, Биолошки факултет, 2014)

TY  - THES
AU  - Stanojlović, Miloš R.
PY  - 2014
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=2839
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:11044/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=99999&RID=1024769714
UR  - http://nardus.mpn.gov.rs/123456789/5281
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8089
AB  - Iako se ishemijske bolesti mozga, koje se karakterišu pogoršanjem motornih i kognitivnih funkcija, uključujući smanjenje sposobnosti učenja i memorije, intenzivno proučavaju poslednjih 20 godina malo je poznato o molekulskim mehanizmima njihovog nastanka,  (...)
AB  - Although ischemic brain diseases, characterized by decline of motor and cognitive functions, including reducing the ability of learning and memory, have been intensively studied over the past 20 years, the molecular mechanisms of their generation, as well  (...)
PB  - Универзитет у Београду, Биолошки факултет
T2  - Универзитет у Београду
T1  - Efekat estradiola u modulaciji apoptotskih signala u moždanoj kori i hipokampusu pacova tokom hronične moždane hipoperfuzije
T1  - Effects of estradiol on modulation of apoptotic signals in cerebral cortex and hippocampus of rats during chronic cerebral hypoperfusion
UR  - https://hdl.handle.net/21.15107/rcub_nardus_5281
ER  - 
@phdthesis{
author = "Stanojlović, Miloš R.",
year = "2014",
abstract = "Iako se ishemijske bolesti mozga, koje se karakterišu pogoršanjem motornih i kognitivnih funkcija, uključujući smanjenje sposobnosti učenja i memorije, intenzivno proučavaju poslednjih 20 godina malo je poznato o molekulskim mehanizmima njihovog nastanka,  (...), Although ischemic brain diseases, characterized by decline of motor and cognitive functions, including reducing the ability of learning and memory, have been intensively studied over the past 20 years, the molecular mechanisms of their generation, as well  (...)",
publisher = "Универзитет у Београду, Биолошки факултет",
journal = "Универзитет у Београду",
title = "Efekat estradiola u modulaciji apoptotskih signala u moždanoj kori i hipokampusu pacova tokom hronične moždane hipoperfuzije, Effects of estradiol on modulation of apoptotic signals in cerebral cortex and hippocampus of rats during chronic cerebral hypoperfusion",
url = "https://hdl.handle.net/21.15107/rcub_nardus_5281"
}
Stanojlović, M. R.. (2014). Efekat estradiola u modulaciji apoptotskih signala u moždanoj kori i hipokampusu pacova tokom hronične moždane hipoperfuzije. in Универзитет у Београду
Универзитет у Београду, Биолошки факултет..
https://hdl.handle.net/21.15107/rcub_nardus_5281
Stanojlović MR. Efekat estradiola u modulaciji apoptotskih signala u moždanoj kori i hipokampusu pacova tokom hronične moždane hipoperfuzije. in Универзитет у Београду. 2014;.
https://hdl.handle.net/21.15107/rcub_nardus_5281 .
Stanojlović, Miloš R., "Efekat estradiola u modulaciji apoptotskih signala u moždanoj kori i hipokampusu pacova tokom hronične moždane hipoperfuzije" in Универзитет у Београду (2014),
https://hdl.handle.net/21.15107/rcub_nardus_5281 .

Developmental Increase in Ecto-5-Nucleotidase Activity Overlaps with Appearance of Two Immunologically Distinct Enzyme Isoforms in Rat Hippocampal Synaptic Plasma Membranes

Grković, Ivana; Bjelobaba, Ivana; Nedeljković, Nadežda; Mitrović, Nataša Lj.; Drakulić, Dunja R.; Stanojlović, Miloš R.; Horvat, Anica

(2014)

TY  - JOUR
AU  - Grković, Ivana
AU  - Bjelobaba, Ivana
AU  - Nedeljković, Nadežda
AU  - Mitrović, Nataša Lj.
AU  - Drakulić, Dunja R.
AU  - Stanojlović, Miloš R.
AU  - Horvat, Anica
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/64
AB  - Ecto-5-nucleotidase (e-5NT), a glycosylphosphatidylinositol-linked membrane protein, catalyzes a conversion of AMP to adenosine, which influences nearly every aspect of brain physiology, including embryonic and postnatal brain development. The present study aimed to investigate a pattern of expression, activity and kinetic properties of e-5NT in the hippocampal formation and synaptic plasma membrane (SPM) preparations in rats at postnatal days (PDs) 7, 15, 20, 30 and 90. By combining gene expression analysis and enzyme histochemistry, we observed that e-5NT mRNA reached the adult level at PD20, while the enzyme activity continued to increase beyond this age. Further analysis revealed that hippocampal layers rich in synapses expressed the highest levels of e-5NT activity, while in layers populated with neuronal cell bodies, the enzyme activity was weak or absent. Therefore, activity and expression of e-5NT were analyzed in SPM preparations isolated from rats at different ages. The presence of two protein bands of about 65 and 68 kDa was determined by immunoblot analysis. The 65-kDa band was present at all ages, and its abundance increased from PD7 to PD20. The 68-kDa band appeared at PD15 and increased until PD30, coinciding with the increase of e-5NT activity, substrate affinity and enzymatic efficiency. Since distinct e-5NT isoforms may derive from different patterns of the enzyme protein N-glycosylation, we speculate that long-term regulation of e-5NT activity in adulthood may be effectuated at posttranslational level and without overall change in the gene and protein expression.
T2  - Journal of Molecular Neuroscience
T1  - Developmental Increase in Ecto-5-Nucleotidase Activity Overlaps with Appearance of Two Immunologically Distinct Enzyme Isoforms in Rat Hippocampal Synaptic Plasma Membranes
VL  - 54
IS  - 1
SP  - 109
EP  - 118
DO  - 10.1007/s12031-014-0256-0
ER  - 
@article{
author = "Grković, Ivana and Bjelobaba, Ivana and Nedeljković, Nadežda and Mitrović, Nataša Lj. and Drakulić, Dunja R. and Stanojlović, Miloš R. and Horvat, Anica",
year = "2014",
abstract = "Ecto-5-nucleotidase (e-5NT), a glycosylphosphatidylinositol-linked membrane protein, catalyzes a conversion of AMP to adenosine, which influences nearly every aspect of brain physiology, including embryonic and postnatal brain development. The present study aimed to investigate a pattern of expression, activity and kinetic properties of e-5NT in the hippocampal formation and synaptic plasma membrane (SPM) preparations in rats at postnatal days (PDs) 7, 15, 20, 30 and 90. By combining gene expression analysis and enzyme histochemistry, we observed that e-5NT mRNA reached the adult level at PD20, while the enzyme activity continued to increase beyond this age. Further analysis revealed that hippocampal layers rich in synapses expressed the highest levels of e-5NT activity, while in layers populated with neuronal cell bodies, the enzyme activity was weak or absent. Therefore, activity and expression of e-5NT were analyzed in SPM preparations isolated from rats at different ages. The presence of two protein bands of about 65 and 68 kDa was determined by immunoblot analysis. The 65-kDa band was present at all ages, and its abundance increased from PD7 to PD20. The 68-kDa band appeared at PD15 and increased until PD30, coinciding with the increase of e-5NT activity, substrate affinity and enzymatic efficiency. Since distinct e-5NT isoforms may derive from different patterns of the enzyme protein N-glycosylation, we speculate that long-term regulation of e-5NT activity in adulthood may be effectuated at posttranslational level and without overall change in the gene and protein expression.",
journal = "Journal of Molecular Neuroscience",
title = "Developmental Increase in Ecto-5-Nucleotidase Activity Overlaps with Appearance of Two Immunologically Distinct Enzyme Isoforms in Rat Hippocampal Synaptic Plasma Membranes",
volume = "54",
number = "1",
pages = "109-118",
doi = "10.1007/s12031-014-0256-0"
}
Grković, I., Bjelobaba, I., Nedeljković, N., Mitrović, N. Lj., Drakulić, D. R., Stanojlović, M. R.,& Horvat, A.. (2014). Developmental Increase in Ecto-5-Nucleotidase Activity Overlaps with Appearance of Two Immunologically Distinct Enzyme Isoforms in Rat Hippocampal Synaptic Plasma Membranes. in Journal of Molecular Neuroscience, 54(1), 109-118.
https://doi.org/10.1007/s12031-014-0256-0
Grković I, Bjelobaba I, Nedeljković N, Mitrović NL, Drakulić DR, Stanojlović MR, Horvat A. Developmental Increase in Ecto-5-Nucleotidase Activity Overlaps with Appearance of Two Immunologically Distinct Enzyme Isoforms in Rat Hippocampal Synaptic Plasma Membranes. in Journal of Molecular Neuroscience. 2014;54(1):109-118.
doi:10.1007/s12031-014-0256-0 .
Grković, Ivana, Bjelobaba, Ivana, Nedeljković, Nadežda, Mitrović, Nataša Lj., Drakulić, Dunja R., Stanojlović, Miloš R., Horvat, Anica, "Developmental Increase in Ecto-5-Nucleotidase Activity Overlaps with Appearance of Two Immunologically Distinct Enzyme Isoforms in Rat Hippocampal Synaptic Plasma Membranes" in Journal of Molecular Neuroscience, 54, no. 1 (2014):109-118,
https://doi.org/10.1007/s12031-014-0256-0 . .
22
18
22

Time-Related Sex Diffrences in Cerebral Hypoperfusion-Induced Brain Injury

Stanojlović, Miloš R.; Guševac, Ivana; Grković, Ivana; Mitrović, Nataša Lj.; Horvat, Anica; Drakulić, Dunja R.

(2014)

TY  - JOUR
AU  - Stanojlović, Miloš R.
AU  - Guševac, Ivana
AU  - Grković, Ivana
AU  - Mitrović, Nataša Lj.
AU  - Horvat, Anica
AU  - Drakulić, Dunja R.
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/301
AB  - Although the model of cerebral hypoperfusion in rats has been a matter of many investigations over the years, the exact intracellular and biochemical mechanisms that lead to neuron loss and memory decline have not been clearly identified. In the current study, we examined whether cerebral hypoperfusion causes changes in hippocampal protein expression of apoptotic markers in the synaptosomal fraction and neurodegeneration in a time-dependent and sex-specific manner. Adult male and female Wistar rats were divided into two main groups, controls that underwent sham operation, and animals subjected to permanent bilateral occlusion of common carotid arteries. Both male and female rats were killed 3, 7 or 90 days following the insult. The obtained results indicate that the peak of processes that lead to apoptosis occured on postoperative day 7 and that they were more prominent in males, indicating that neuroprotective effects of certain substances (planned for future experiments), should be tested at this time point.
T2  - Archives of Biological Sciences
T1  - Time-Related Sex Diffrences in Cerebral Hypoperfusion-Induced Brain Injury
VL  - 66
IS  - 4
SP  - 1673
EP  - 1680
DO  - 10.2298/ABS1404673S
ER  - 
@article{
author = "Stanojlović, Miloš R. and Guševac, Ivana and Grković, Ivana and Mitrović, Nataša Lj. and Horvat, Anica and Drakulić, Dunja R.",
year = "2014",
abstract = "Although the model of cerebral hypoperfusion in rats has been a matter of many investigations over the years, the exact intracellular and biochemical mechanisms that lead to neuron loss and memory decline have not been clearly identified. In the current study, we examined whether cerebral hypoperfusion causes changes in hippocampal protein expression of apoptotic markers in the synaptosomal fraction and neurodegeneration in a time-dependent and sex-specific manner. Adult male and female Wistar rats were divided into two main groups, controls that underwent sham operation, and animals subjected to permanent bilateral occlusion of common carotid arteries. Both male and female rats were killed 3, 7 or 90 days following the insult. The obtained results indicate that the peak of processes that lead to apoptosis occured on postoperative day 7 and that they were more prominent in males, indicating that neuroprotective effects of certain substances (planned for future experiments), should be tested at this time point.",
journal = "Archives of Biological Sciences",
title = "Time-Related Sex Diffrences in Cerebral Hypoperfusion-Induced Brain Injury",
volume = "66",
number = "4",
pages = "1673-1680",
doi = "10.2298/ABS1404673S"
}
Stanojlović, M. R., Guševac, I., Grković, I., Mitrović, N. Lj., Horvat, A.,& Drakulić, D. R.. (2014). Time-Related Sex Diffrences in Cerebral Hypoperfusion-Induced Brain Injury. in Archives of Biological Sciences, 66(4), 1673-1680.
https://doi.org/10.2298/ABS1404673S
Stanojlović MR, Guševac I, Grković I, Mitrović NL, Horvat A, Drakulić DR. Time-Related Sex Diffrences in Cerebral Hypoperfusion-Induced Brain Injury. in Archives of Biological Sciences. 2014;66(4):1673-1680.
doi:10.2298/ABS1404673S .
Stanojlović, Miloš R., Guševac, Ivana, Grković, Ivana, Mitrović, Nataša Lj., Horvat, Anica, Drakulić, Dunja R., "Time-Related Sex Diffrences in Cerebral Hypoperfusion-Induced Brain Injury" in Archives of Biological Sciences, 66, no. 4 (2014):1673-1680,
https://doi.org/10.2298/ABS1404673S . .
4
3
4