TY  - JOUR
AU  - Dragić, Milorad
AU  - Mihajlovic, Katarina
AU  - Adžić, Marija
AU  - Jakovljević, Marija
AU  - Zarić Kontić, Marina
AU  - Mitrović, Nataša
AU  - Laketa, Danijela
AU  - Lavrnja, Irena
AU  - Kipp, Markus
AU  - Grković, Ivana
AU  - Nedeljkovic, Nadezda
PY  - 2022
UR  - http://journals.sagepub.com/doi/10.1177/17590914221102068
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4984
AB  - Ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2) hydrolyzes extracellular ATP to ADP, which is the ligand for P2Y1,12,13 receptors. The present study describes the distribution of NTPDase2 in adult rat brains in physiological conditions, and in hippocampal neurodegeneration induced by trimethyltin (TMT). The study also describes the regulation of NTPDase2 by inflammatory mediators in primary astrocytes and oligodendroglial cell line OLN93. In physiological conditions, NTPDase2 protein was most abundant in the hippocampus, where it was found in fibrous astrocytes and synaptic endings in the synaptic-rich hippocampal layers. In TMT-induced neurodegeneration, NTPDase2-mRNA acutely decreased at 2-dpi and then gradually recovered to the control level at 7-dpi and 21-dpi. As determined by immunohistochemistry and double immunofluorescence, the decrease was most pronounced in the dentate gyrus (DG), where NTPDase2 withdrew from the synaptic boutons in the polymorphic layer of DG, whereas the recovery of the expression was most profound in the subgranular layer. Concerning the regulation of NTPDase2 gene expression, proinflammatory cytokines IL-6, IL-1β, TNFα, and IFNγ negatively regulated the expression of NTPDase2 in OLN93 cells, while did not altering the expression in primary astrocytes. Different cell-intrinsic stressors, such as depletion of intracellular energy store, oxidative stress, endoplasmic reticulum stress, and activation of protein kinase C, also massively disturbed the expression of the NTPDase2 gene. Together, our results suggest that the expression and the activity of NTPDase2 transiently cease in neurodegeneration and brain injury, most likely as a part of the acute adaptive response designed to promote cell defense, survival, and recovery.
T2  - ASN Neuro
T1  - Expression of Ectonucleoside Triphosphate Diphosphohydrolase 2 (NTPDase2) Is Negatively Regulated Under Neuroinflammatory Conditions In Vivo and In Vitro.
VL  - 14
DO  - 10.1177/17590914221102068
SP  - 17590914221102068
ER  - 

@article{
author = "Dragić, Milorad and Mihajlovic, Katarina and Adžić, Marija and Jakovljević, Marija and Zarić Kontić, Marina and Mitrović, Nataša and Laketa, Danijela and Lavrnja, Irena and Kipp, Markus and Grković, Ivana and Nedeljkovic, Nadezda",
year = "2022",
abstract = "Ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2) hydrolyzes extracellular ATP to ADP, which is the ligand for P2Y1,12,13 receptors. The present study describes the distribution of NTPDase2 in adult rat brains in physiological conditions, and in hippocampal neurodegeneration induced by trimethyltin (TMT). The study also describes the regulation of NTPDase2 by inflammatory mediators in primary astrocytes and oligodendroglial cell line OLN93. In physiological conditions, NTPDase2 protein was most abundant in the hippocampus, where it was found in fibrous astrocytes and synaptic endings in the synaptic-rich hippocampal layers. In TMT-induced neurodegeneration, NTPDase2-mRNA acutely decreased at 2-dpi and then gradually recovered to the control level at 7-dpi and 21-dpi. As determined by immunohistochemistry and double immunofluorescence, the decrease was most pronounced in the dentate gyrus (DG), where NTPDase2 withdrew from the synaptic boutons in the polymorphic layer of DG, whereas the recovery of the expression was most profound in the subgranular layer. Concerning the regulation of NTPDase2 gene expression, proinflammatory cytokines IL-6, IL-1β, TNFα, and IFNγ negatively regulated the expression of NTPDase2 in OLN93 cells, while did not altering the expression in primary astrocytes. Different cell-intrinsic stressors, such as depletion of intracellular energy store, oxidative stress, endoplasmic reticulum stress, and activation of protein kinase C, also massively disturbed the expression of the NTPDase2 gene. Together, our results suggest that the expression and the activity of NTPDase2 transiently cease in neurodegeneration and brain injury, most likely as a part of the acute adaptive response designed to promote cell defense, survival, and recovery.",
journal = "ASN Neuro",
title = "Expression of Ectonucleoside Triphosphate Diphosphohydrolase 2 (NTPDase2) Is Negatively Regulated Under Neuroinflammatory Conditions In Vivo and In Vitro.",
volume = "14",
doi = "10.1177/17590914221102068",
pages = "17590914221102068"
}

Dragić, M., Mihajlovic, K., Adžić, M., Jakovljević, M., Zarić Kontić, M., Mitrović, N., Laketa, D., Lavrnja, I., Kipp, M., Grković, I.,& Nedeljkovic, N.. (2022). Expression of Ectonucleoside Triphosphate Diphosphohydrolase 2 (NTPDase2) Is Negatively Regulated Under Neuroinflammatory Conditions In Vivo and In Vitro.. in ASN Neuro, 14, 17590914221102068.
https://doi.org/10.1177/17590914221102068

Dragić M, Mihajlovic K, Adžić M, Jakovljević M, Zarić Kontić M, Mitrović N, Laketa D, Lavrnja I, Kipp M, Grković I, Nedeljkovic N. Expression of Ectonucleoside Triphosphate Diphosphohydrolase 2 (NTPDase2) Is Negatively Regulated Under Neuroinflammatory Conditions In Vivo and In Vitro.. in ASN Neuro. 2022;14:17590914221102068.
doi:10.1177/17590914221102068 .

Dragić, Milorad, Mihajlovic, Katarina, Adžić, Marija, Jakovljević, Marija, Zarić Kontić, Marina, Mitrović, Nataša, Laketa, Danijela, Lavrnja, Irena, Kipp, Markus, Grković, Ivana, Nedeljkovic, Nadezda, "Expression of Ectonucleoside Triphosphate Diphosphohydrolase 2 (NTPDase2) Is Negatively Regulated Under Neuroinflammatory Conditions In Vivo and In Vitro." in ASN Neuro, 14 (2022):17590914221102068,
https://doi.org/10.1177/17590914221102068 . .

TY  - CONF
AU  - Guševac Stojanović, Ivana
AU  - Todorović, Ana
AU  - Pejić, Snežana
AU  - Tatalović, Nikola
AU  - Blagojević, Duško
AU  - Martinović, Jelena
AU  - Grković, Ivana
AU  - Mitrović, Nataša
AU  - Zarić, Marina
AU  - Drakulić, Dunja
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5247
AB  - Numerous natural compounds, like progesterone (P4), a sex steroid hormone, are highlighted as promising agents for treatment of different disorders including prolonged disturbance of blood flow. However, its action on several oxidative stress markers (pro/antioxidant balance, products of lipid peroxidation and phosphatidylcholine to lysophosphatidylcholine intensity ratio) and one of the major components of antioxidant system, superoxide dismutase in rat prefrontal cortex (PFC) following permanent bilateral occlusion of common carotid arteries (2VO) is not completely investigated. According to the obtained results, levels of investigated oxidative stress markers and SOD activity were altered in 2VO animals treated with vehicle, while P4 treatment returned them to control values. Overall, presented data indicate that P4 might manifest antioxidative features in PFC of 2VO rats.
PB  - Belgrade: Society of Physical Chemists of Serbia
C3  - Proceeding: 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2021: the Conference is dedicated to the 30th Anniversary of the founding of the Society of Physical Chemists of Serbia and 100th Anniversary of Bray-Liebhafsky reaction. Vol. 1; 2021 Sep 20-24; Belgrade, Serbia
T1  - Cerebral hypoperfusion and progesterone treatment alter parameters of oxidative stress and antioxidant defence in male rats
VL  - 1
SP  - 25
EP  - 32
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5247
ER  - 

@conference{
author = "Guševac Stojanović, Ivana and Todorović, Ana and Pejić, Snežana and Tatalović, Nikola and Blagojević, Duško and Martinović, Jelena and Grković, Ivana and Mitrović, Nataša and Zarić, Marina and Drakulić, Dunja",
year = "2021",
abstract = "Numerous natural compounds, like progesterone (P4), a sex steroid hormone, are highlighted as promising agents for treatment of different disorders including prolonged disturbance of blood flow. However, its action on several oxidative stress markers (pro/antioxidant balance, products of lipid peroxidation and phosphatidylcholine to lysophosphatidylcholine intensity ratio) and one of the major components of antioxidant system, superoxide dismutase in rat prefrontal cortex (PFC) following permanent bilateral occlusion of common carotid arteries (2VO) is not completely investigated. According to the obtained results, levels of investigated oxidative stress markers and SOD activity were altered in 2VO animals treated with vehicle, while P4 treatment returned them to control values. Overall, presented data indicate that P4 might manifest antioxidative features in PFC of 2VO rats.",
publisher = "Belgrade: Society of Physical Chemists of Serbia",
journal = "Proceeding: 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2021: the Conference is dedicated to the 30th Anniversary of the founding of the Society of Physical Chemists of Serbia and 100th Anniversary of Bray-Liebhafsky reaction. Vol. 1; 2021 Sep 20-24; Belgrade, Serbia",
title = "Cerebral hypoperfusion and progesterone treatment alter parameters of oxidative stress and antioxidant defence in male rats",
volume = "1",
pages = "25-32",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5247"
}

Guševac Stojanović, I., Todorović, A., Pejić, S., Tatalović, N., Blagojević, D., Martinović, J., Grković, I., Mitrović, N., Zarić, M.,& Drakulić, D.. (2021). Cerebral hypoperfusion and progesterone treatment alter parameters of oxidative stress and antioxidant defence in male rats. in Proceeding: 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2021: the Conference is dedicated to the 30th Anniversary of the founding of the Society of Physical Chemists of Serbia and 100th Anniversary of Bray-Liebhafsky reaction. Vol. 1; 2021 Sep 20-24; Belgrade, Serbia
Belgrade: Society of Physical Chemists of Serbia., 1, 25-32.
https://hdl.handle.net/21.15107/rcub_ibiss_5247

Guševac Stojanović I, Todorović A, Pejić S, Tatalović N, Blagojević D, Martinović J, Grković I, Mitrović N, Zarić M, Drakulić D. Cerebral hypoperfusion and progesterone treatment alter parameters of oxidative stress and antioxidant defence in male rats. in Proceeding: 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2021: the Conference is dedicated to the 30th Anniversary of the founding of the Society of Physical Chemists of Serbia and 100th Anniversary of Bray-Liebhafsky reaction. Vol. 1; 2021 Sep 20-24; Belgrade, Serbia. 2021;1:25-32.
https://hdl.handle.net/21.15107/rcub_ibiss_5247 .

Guševac Stojanović, Ivana, Todorović, Ana, Pejić, Snežana, Tatalović, Nikola, Blagojević, Duško, Martinović, Jelena, Grković, Ivana, Mitrović, Nataša, Zarić, Marina, Drakulić, Dunja, "Cerebral hypoperfusion and progesterone treatment alter parameters of oxidative stress and antioxidant defence in male rats" in Proceeding: 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2021: the Conference is dedicated to the 30th Anniversary of the founding of the Society of Physical Chemists of Serbia and 100th Anniversary of Bray-Liebhafsky reaction. Vol. 1; 2021 Sep 20-24; Belgrade, Serbia, 1 (2021):25-32,
https://hdl.handle.net/21.15107/rcub_ibiss_5247 .

TY  - CONF
AU  - Guševac, Ivana
AU  - Tatalović, Nikola
AU  - Zarić, Marina
AU  - Martinović, Jelena
AU  - Mitrović, Nataša
AU  - Blagojević, Duško
AU  - Grković, Ivana
AU  - Drakulić, Dunja
PY  - 2018
UR  - https://forum2018.fens.org/
UR  - https://radar.ibiss.bg.ac.rs/123456789/3897
AB  - Potent neurosteroid progesterone (P4) strongly influences functional recovery in
various models of neurological diseases. However, its protective antioxidative
potential is not well established in stance of chronic cerebral hypoperfusion (CCH)
that induces ischemic milieu in the brain. CCH results in a cascade of events
leading to uncontrolled generation of 4-hydroxynonenal (HNE), a hallmark of
oxidative stress that can be abolished by mitochondrial antioxidant enzyme
manganese superoxide dismutase (MnSOD). Post-ischemic brain regeneration
requires preservation of cerebral blood flow that could be achieved by production of
vasodilatator nitric oxide (NO), synthesized by endothelial NO synthase (eNOS)
whose actions are regulated by phosphorylation at various sites. Decreased
phosphorylation of eNOS at Thr495 during antioxidative response, promotes its
activity and NO production, contributing to neuroprotection. Given the scarcity of
data about P4 antioxidative actions in prefrontal cortex during CCH, current study
assessed the level of HNE and NO, as well as MnSOD activity and the extent of
eNOS phosphorylation at Thr495 in rats subjected to sham operation and injected
with vehicle (commercial flax oil) or animals with permanent occlusion of common
carotid arteries and treated either with vehicle or P4 (1.7 mg/kg/day) for 7 days.
Results indicate that P4 decreases CCH-induced HNE generation and MnSOD
activity, diminishes inactivation of eNOS and increases production of protective NO.
In conclusion, P4 might downscale oxidative stress and boost antioxidant defense
capacity in CCH model, pointing investigated parameters as potential targets of P4
neuroprotective actions. Financially supported by MNTPR RS, grants 173044 and
41014.
PB  - Brussels, Belgium : Federation of European Neurocience Societies
C3  - 11th FENS Forum of Neuroscience
T1  - Progesterone downscales oxidative stress and boosts antioxidant defense capacity in rat model of permanent common carotid artery occlusion
SP  - 1971
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3897
ER  - 

@conference{
author = "Guševac, Ivana and Tatalović, Nikola and Zarić, Marina and Martinović, Jelena and Mitrović, Nataša and Blagojević, Duško and Grković, Ivana and Drakulić, Dunja",
year = "2018",
abstract = "Potent neurosteroid progesterone (P4) strongly influences functional recovery in
various models of neurological diseases. However, its protective antioxidative
potential is not well established in stance of chronic cerebral hypoperfusion (CCH)
that induces ischemic milieu in the brain. CCH results in a cascade of events
leading to uncontrolled generation of 4-hydroxynonenal (HNE), a hallmark of
oxidative stress that can be abolished by mitochondrial antioxidant enzyme
manganese superoxide dismutase (MnSOD). Post-ischemic brain regeneration
requires preservation of cerebral blood flow that could be achieved by production of
vasodilatator nitric oxide (NO), synthesized by endothelial NO synthase (eNOS)
whose actions are regulated by phosphorylation at various sites. Decreased
phosphorylation of eNOS at Thr495 during antioxidative response, promotes its
activity and NO production, contributing to neuroprotection. Given the scarcity of
data about P4 antioxidative actions in prefrontal cortex during CCH, current study
assessed the level of HNE and NO, as well as MnSOD activity and the extent of
eNOS phosphorylation at Thr495 in rats subjected to sham operation and injected
with vehicle (commercial flax oil) or animals with permanent occlusion of common
carotid arteries and treated either with vehicle or P4 (1.7 mg/kg/day) for 7 days.
Results indicate that P4 decreases CCH-induced HNE generation and MnSOD
activity, diminishes inactivation of eNOS and increases production of protective NO.
In conclusion, P4 might downscale oxidative stress and boost antioxidant defense
capacity in CCH model, pointing investigated parameters as potential targets of P4
neuroprotective actions. Financially supported by MNTPR RS, grants 173044 and
41014.",
publisher = "Brussels, Belgium : Federation of European Neurocience Societies",
journal = "11th FENS Forum of Neuroscience",
title = "Progesterone downscales oxidative stress and boosts antioxidant defense capacity in rat model of permanent common carotid artery occlusion",
pages = "1971",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3897"
}

Guševac, I., Tatalović, N., Zarić, M., Martinović, J., Mitrović, N., Blagojević, D., Grković, I.,& Drakulić, D.. (2018). Progesterone downscales oxidative stress and boosts antioxidant defense capacity in rat model of permanent common carotid artery occlusion. in 11th FENS Forum of Neuroscience
Brussels, Belgium : Federation of European Neurocience Societies., 1971.
https://hdl.handle.net/21.15107/rcub_ibiss_3897

Guševac I, Tatalović N, Zarić M, Martinović J, Mitrović N, Blagojević D, Grković I, Drakulić D. Progesterone downscales oxidative stress and boosts antioxidant defense capacity in rat model of permanent common carotid artery occlusion. in 11th FENS Forum of Neuroscience. 2018;:1971.
https://hdl.handle.net/21.15107/rcub_ibiss_3897 .

Guševac, Ivana, Tatalović, Nikola, Zarić, Marina, Martinović, Jelena, Mitrović, Nataša, Blagojević, Duško, Grković, Ivana, Drakulić, Dunja, "Progesterone downscales oxidative stress and boosts antioxidant defense capacity in rat model of permanent common carotid artery occlusion" in 11th FENS Forum of Neuroscience (2018):1971,
https://hdl.handle.net/21.15107/rcub_ibiss_3897 .

TY  - JOUR
AU  - Grković, Ivana
AU  - Bjelobaba, Ivana
AU  - Mitrović, Nataša
AU  - Lavrnja, Irena
AU  - Drakulić, Dunja
AU  - Martinović, Jelena
AU  - Stanojlović, Miloš
AU  - Horvat, Anica
AU  - Nedeljković, Nadežda
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5977
AB  - Nucleoside triphosphate diphosphohydrolase3 (NTPDase3) is membrane-bound ectoenzyme which hydrolyzes extracellular ATP, thus modulating the function of purinergicreceptors and the pattern of purinergic signaling. Here we analyzed the developmentalexpression of NTPDase3 in female hypothalamus, cerebral cortex and hippocampal formationat different postnatal ages (PD7–PD90) by qRT-PCR and immunohistochemistry. Inhypothalamus and hippocampus, a similar developmental profile was seen: NTPDase3 geneexpression was stable during postnatal development and increased in adults. In the cortex,upregulation of NTPDase3 mRNA expression was seen at PD15 and further increase wasevidenced in adults. Immunohistochemical analysis at PD7 revealed faint neuronal NTPDase3localization, in dorsal hypothalamus. The immunoreactivity (ir) gradually increased in PD15and 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 posteriorhypothalamic area, while in PD30 the fibers appeared progressively longer and markedlyvaricose. In adults, the strongest NTPDase3-ir was observed in collections of cells indorsomedial hypothalamic nucleus, dorsal and lateral hypothalamus and in several thalamicareas, whereas the varicose fibers traversed entire diencephalon, particularly paraventricularthalamic nucleus, ventromedial and dorsomedial hypothalamic nuclei, the arcuate nucleus andthe prefornical part of the lateral hypothalamus. The presumably ascending NTPDase3-irfibers were first observed in PD20; their density and the varicose appearance increased untilthe adulthood. Prominent enhancement of NTPDase3-ir in the hypothalamus coincides withage when animals acquire diurnal rhythms of sleeping and feeding, supporting the hypothesisthat this enzyme may be involved in regulation of homeostatic functions.
PB  - Amsterdam: Elsevier Science Publisher
T2  - Journal of chemical neuroanatomy
T1  - Expression of ecto-nucleoside triphosphate diphosphohydrolase3 (NTPDase3) in the female rat brain during postnatal development
VL  - 77
DO  - 10.1016/j.jchemneu.2016.04.001
SP  - 10
EP  - 18
ER  - 

@article{
author = "Grković, Ivana and Bjelobaba, Ivana and Mitrović, Nataša and Lavrnja, Irena and Drakulić, Dunja and Martinović, Jelena and Stanojlović, Miloš and Horvat, Anica and Nedeljković, Nadežda",
year = "2016",
abstract = "Nucleoside triphosphate diphosphohydrolase3 (NTPDase3) is membrane-bound ectoenzyme which hydrolyzes extracellular ATP, thus modulating the function of purinergicreceptors and the pattern of purinergic signaling. Here we analyzed the developmentalexpression of NTPDase3 in female hypothalamus, cerebral cortex and hippocampal formationat different postnatal ages (PD7–PD90) by qRT-PCR and immunohistochemistry. Inhypothalamus and hippocampus, a similar developmental profile was seen: NTPDase3 geneexpression was stable during postnatal development and increased in adults. In the cortex,upregulation of NTPDase3 mRNA expression was seen at PD15 and further increase wasevidenced in adults. Immunohistochemical analysis at PD7 revealed faint neuronal NTPDase3localization, in dorsal hypothalamus. The immunoreactivity (ir) gradually increased in PD15and 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 posteriorhypothalamic area, while in PD30 the fibers appeared progressively longer and markedlyvaricose. In adults, the strongest NTPDase3-ir was observed in collections of cells indorsomedial hypothalamic nucleus, dorsal and lateral hypothalamus and in several thalamicareas, whereas the varicose fibers traversed entire diencephalon, particularly paraventricularthalamic nucleus, ventromedial and dorsomedial hypothalamic nuclei, the arcuate nucleus andthe prefornical part of the lateral hypothalamus. The presumably ascending NTPDase3-irfibers were first observed in PD20; their density and the varicose appearance increased untilthe adulthood. Prominent enhancement of NTPDase3-ir in the hypothalamus coincides withage when animals acquire diurnal rhythms of sleeping and feeding, supporting the hypothesisthat this enzyme may be involved in regulation of homeostatic functions.",
publisher = "Amsterdam: Elsevier Science Publisher",
journal = "Journal of chemical neuroanatomy",
title = "Expression of ecto-nucleoside triphosphate diphosphohydrolase3 (NTPDase3) in the female rat brain during postnatal development",
volume = "77",
doi = "10.1016/j.jchemneu.2016.04.001",
pages = "10-18"
}

Grković, I., Bjelobaba, I., Mitrović, N., Lavrnja, I., Drakulić, D., Martinović, J., Stanojlović, M., 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
Amsterdam: Elsevier Science Publisher., 77, 10-18.
https://doi.org/10.1016/j.jchemneu.2016.04.001

Grković I, Bjelobaba I, Mitrović N, Lavrnja I, Drakulić D, Martinović J, Stanojlović M, 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, Lavrnja, Irena, Drakulić, Dunja, Martinović, Jelena, Stanojlović, Miloš, Horvat, Anica, Nedeljković, Nadežda, "Expression of ecto-nucleoside triphosphate diphosphohydrolase3 (NTPDase3) in the female rat brain during postnatal development" in Journal of chemical neuroanatomy, 77 (2016):10-18,
https://doi.org/10.1016/j.jchemneu.2016.04.001 . .

TY  - JOUR
AU  - Grković, Ivana
AU  - Bjelobaba, Ivana
AU  - Mitrović, Nataša
AU  - Lavrnja, Irena
AU  - Drakulić, Dunja
AU  - Martinović, Jelena
AU  - Stanojlović, Miloš
AU  - Horvat, Anica
AU  - Nedeljković, Nadežda
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5976
AB  - Nucleoside triphosphate diphosphohydrolase3 (NTPDase3) is membrane-bound ectoenzyme 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 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.
PB  - Amsterdam: Elsevier Science Publisher
T2  - Journal of chemical neuroanatomy
T1  - Expression of ecto-nucleoside triphosphate diphosphohydrolase3 (NTPDase3) in the female rat brain during postnatal development
VL  - 77
DO  - 10.1016/j.jchemneu.2016.04.001
SP  - 10
EP  - 18
ER  - 

@article{
author = "Grković, Ivana and Bjelobaba, Ivana and Mitrović, Nataša and Lavrnja, Irena and Drakulić, Dunja and Martinović, Jelena and Stanojlović, Miloš and Horvat, Anica and Nedeljković, Nadežda",
year = "2016",
abstract = "Nucleoside triphosphate diphosphohydrolase3 (NTPDase3) is membrane-bound ectoenzyme 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 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.",
publisher = "Amsterdam: Elsevier Science Publisher",
journal = "Journal of chemical neuroanatomy",
title = "Expression of ecto-nucleoside triphosphate diphosphohydrolase3 (NTPDase3) in the female rat brain during postnatal development",
volume = "77",
doi = "10.1016/j.jchemneu.2016.04.001",
pages = "10-18"
}

Grković, I., Bjelobaba, I., Mitrović, N., Lavrnja, I., Drakulić, D., Martinović, J., Stanojlović, M., 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
Amsterdam: Elsevier Science Publisher., 77, 10-18.
https://doi.org/10.1016/j.jchemneu.2016.04.001

Grković I, Bjelobaba I, Mitrović N, Lavrnja I, Drakulić D, Martinović J, Stanojlović M, 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, Lavrnja, Irena, Drakulić, Dunja, Martinović, Jelena, Stanojlović, Miloš, Horvat, Anica, Nedeljković, Nadežda, "Expression of ecto-nucleoside triphosphate diphosphohydrolase3 (NTPDase3) in the female rat brain during postnatal development" in Journal of chemical neuroanatomy, 77 (2016):10-18,
https://doi.org/10.1016/j.jchemneu.2016.04.001 . .

TY  - JOUR
AU  - Drakulić, Dunja R
AU  - Veličković, Nataša
AU  - Stanojlović, Milos  R
AU  - Grković, Ivana S
AU  - Mitrović, N
AU  - Lavrnja, Irena
AU  - Horvat, Anica I
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/994
AB  - Synthetic glucocorticoid dexamethasone (DEX), a highly potent anti-inflammatory and immunosuppressive agent, is widely used in the treatment of brain cancer, as well as for inflammatory and autoimmune diseases. The present study aimed to determine whether low-dose subchronic DEX treatment (100g/kg for eight consecutive days) exerts long-term effects on apoptosis in the adult rat prefrontal cortex (PFC) by examining the expression of cell death-promoting molecules [poly(ADP-ribose) polymerase (PARP), p53, procaspase 3, cleaved caspase 3, Bax] and cell-survival molecules (AKT, Bcl-2). The results obtained revealed that body, thymus and adrenal gland weights, as well corticosterone levels, in the serum and PFC were reduced 1day after the last DEX injection. In the PFC, DEX caused activation of AKT, augmentation of pro-survival Bcl-2 protein and an enhanced Bcl-2/Bax protein ratio, as well Bcl-2 translocation to the mitochondria. An unaltered profile with respect to the protein expression of apoptotic molecules PARP, procaspase 3 and Bax was detected, whereas p53 protein was decreased. Reverse transcriptase -polymerase chain reaction analysis showed a decrease of p53 mRNA levels and no significant difference in Bcl-2 and Bax mRNA expression in DEX-treated rats. Finally, a DNA fragmentation assay and Fluoro-Jade staining demonstrated no considerable changes in apoptosis in the rat PFC. Our findings support the concept that low-dose DEX creates a hypocorticoid state in the brain and also indicate that subchronic DEX treatment activates the pro-survival signalling pathway but does not change apoptotic markers in the rat PFC. This mechanism might be relevant for the DEX-induced apoptosis resistance observed during and after chemotherapy of patients with brain tumours.
T2  - Journal of Neuroendocrinology
T1  - Low-Dose Dexamethasone Treatment Promotes the Pro-Survival Signalling Pathway in the Adult Rat Prefrontal Cortex
IS  - 7
VL  - 25
SP  - 125
EP  - 616
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_994
ER  - 

@article{
author = "Drakulić, Dunja R and Veličković, Nataša and Stanojlović, Milos  R and Grković, Ivana S and Mitrović, N and Lavrnja, Irena and Horvat, Anica I",
year = "2013",
abstract = "Synthetic glucocorticoid dexamethasone (DEX), a highly potent anti-inflammatory and immunosuppressive agent, is widely used in the treatment of brain cancer, as well as for inflammatory and autoimmune diseases. The present study aimed to determine whether low-dose subchronic DEX treatment (100g/kg for eight consecutive days) exerts long-term effects on apoptosis in the adult rat prefrontal cortex (PFC) by examining the expression of cell death-promoting molecules [poly(ADP-ribose) polymerase (PARP), p53, procaspase 3, cleaved caspase 3, Bax] and cell-survival molecules (AKT, Bcl-2). The results obtained revealed that body, thymus and adrenal gland weights, as well corticosterone levels, in the serum and PFC were reduced 1day after the last DEX injection. In the PFC, DEX caused activation of AKT, augmentation of pro-survival Bcl-2 protein and an enhanced Bcl-2/Bax protein ratio, as well Bcl-2 translocation to the mitochondria. An unaltered profile with respect to the protein expression of apoptotic molecules PARP, procaspase 3 and Bax was detected, whereas p53 protein was decreased. Reverse transcriptase -polymerase chain reaction analysis showed a decrease of p53 mRNA levels and no significant difference in Bcl-2 and Bax mRNA expression in DEX-treated rats. Finally, a DNA fragmentation assay and Fluoro-Jade staining demonstrated no considerable changes in apoptosis in the rat PFC. Our findings support the concept that low-dose DEX creates a hypocorticoid state in the brain and also indicate that subchronic DEX treatment activates the pro-survival signalling pathway but does not change apoptotic markers in the rat PFC. This mechanism might be relevant for the DEX-induced apoptosis resistance observed during and after chemotherapy of patients with brain tumours.",
journal = "Journal of Neuroendocrinology",
title = "Low-Dose Dexamethasone Treatment Promotes the Pro-Survival Signalling Pathway in the Adult Rat Prefrontal Cortex",
number = "7",
volume = "25",
pages = "125-616",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_994"
}

Drakulić, D. R., Veličković, N., Stanojlović, Milos  R, Grković, I. S., Mitrović, N., Lavrnja, I.,& Horvat, A. I.. (2013). Low-Dose Dexamethasone Treatment Promotes the Pro-Survival Signalling Pathway in the Adult Rat Prefrontal Cortex. in Journal of Neuroendocrinology, 25(7), 125-616.
https://hdl.handle.net/21.15107/rcub_ibiss_994

Drakulić DR, Veličković N, Stanojlović, Milos  R, Grković IS, Mitrović N, Lavrnja I, Horvat AI. Low-Dose Dexamethasone Treatment Promotes the Pro-Survival Signalling Pathway in the Adult Rat Prefrontal Cortex. in Journal of Neuroendocrinology. 2013;25(7):125-616.
https://hdl.handle.net/21.15107/rcub_ibiss_994 .

Drakulić, Dunja R, Veličković, Nataša, Stanojlović, Milos  R, Grković, Ivana S, Mitrović, N, Lavrnja, Irena, Horvat, Anica I, "Low-Dose Dexamethasone Treatment Promotes the Pro-Survival Signalling Pathway in the Adult Rat Prefrontal Cortex" in Journal of Neuroendocrinology, 25, no. 7 (2013):125-616,
https://hdl.handle.net/21.15107/rcub_ibiss_994 .

TY  - JOUR
AU  - Veličković, Nataša
AU  - Drakulić, Dunja R
AU  - Petrović, Snjezana B
AU  - Grković, Ivana S
AU  - Milosević, Maja S
AU  - Stanojlović, Milos  R
AU  - Horvat, Anica I
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1104
AB  - Recent studies reported that exposure of juvenile rats to cranial irradiation affects hypothalamic-pituitary-adrenal (HPA) axis stability, leading to its activation along with radiation-induced inflammation. In the present study, we hypothesized whether inflammatory reaction in the CNS could be a mediator of HPA axis response to cranial irradiation (CI). Therefore, we analyzed time-course changes of serum corticosterone level, as well IL-1 beta and TNF-alpha level in the serum and hypothalamus of juvenile rats after CI. Protein and gene expression of the glucocorticoid receptor (GR) and nuclear factor kappaB (NF kappa B) were examined in the hippocampus within 24 h postirradiation interval. Cranial irradiation led to rapid induction of both GR and NF kappa B mRNA and protein in the hippocampus at 1 h. The increment in NF kappa B protein persisted for 2 h, therefore NF kappa B/GR protein ratio was turned in favor of NF kappa B. Central inflammation was characterized by increased IL-1 beta in the hypothalamus, with maximum levels at 2 and 4 h after irradiation, while both IL-1 beta and TNF-alpha were undetectable in the serum. Enhanced hypothalamic IL-1 beta probably induced the relocation of hippocampal NF kappa B to the nucleus and decreased NF kappa B mRNA at 6 h, indicating promotion of inflammation in the key tissue for HPA axis regulation. Concomitant increase of corticosterone level and enhanced GR nuclear translocation in the hippocampus at 6 h might represent a compensatory mechanism for observed inflammation. Our results indicate that acute radiation response is characterized by increased central inflammation and concomitant HPA axis activation, most likely having a role in protection of the organism from overwhelming inflammatory reaction.
T2  - Cellular and Molecular Neurobiology
T1  - Time-Course of Hypothalamic-Pituitary-Adrenal Axis Activity and Inflammation in Juvenile Rat Brain After Cranial Irradiation
IS  - 7
VL  - 32
SP  - 129
EP  - 1185
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1104
ER  - 

@article{
author = "Veličković, Nataša and Drakulić, Dunja R and Petrović, Snjezana B and Grković, Ivana S and Milosević, Maja S and Stanojlović, Milos  R and Horvat, Anica I",
year = "2012",
abstract = "Recent studies reported that exposure of juvenile rats to cranial irradiation affects hypothalamic-pituitary-adrenal (HPA) axis stability, leading to its activation along with radiation-induced inflammation. In the present study, we hypothesized whether inflammatory reaction in the CNS could be a mediator of HPA axis response to cranial irradiation (CI). Therefore, we analyzed time-course changes of serum corticosterone level, as well IL-1 beta and TNF-alpha level in the serum and hypothalamus of juvenile rats after CI. Protein and gene expression of the glucocorticoid receptor (GR) and nuclear factor kappaB (NF kappa B) were examined in the hippocampus within 24 h postirradiation interval. Cranial irradiation led to rapid induction of both GR and NF kappa B mRNA and protein in the hippocampus at 1 h. The increment in NF kappa B protein persisted for 2 h, therefore NF kappa B/GR protein ratio was turned in favor of NF kappa B. Central inflammation was characterized by increased IL-1 beta in the hypothalamus, with maximum levels at 2 and 4 h after irradiation, while both IL-1 beta and TNF-alpha were undetectable in the serum. Enhanced hypothalamic IL-1 beta probably induced the relocation of hippocampal NF kappa B to the nucleus and decreased NF kappa B mRNA at 6 h, indicating promotion of inflammation in the key tissue for HPA axis regulation. Concomitant increase of corticosterone level and enhanced GR nuclear translocation in the hippocampus at 6 h might represent a compensatory mechanism for observed inflammation. Our results indicate that acute radiation response is characterized by increased central inflammation and concomitant HPA axis activation, most likely having a role in protection of the organism from overwhelming inflammatory reaction.",
journal = "Cellular and Molecular Neurobiology",
title = "Time-Course of Hypothalamic-Pituitary-Adrenal Axis Activity and Inflammation in Juvenile Rat Brain After Cranial Irradiation",
number = "7",
volume = "32",
pages = "129-1185",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1104"
}

Veličković, N., Drakulić, D. R., Petrović, S. B., Grković, I. S., Milosević, M. S., Stanojlović, Milos  R,& Horvat, A. I.. (2012). Time-Course of Hypothalamic-Pituitary-Adrenal Axis Activity and Inflammation in Juvenile Rat Brain After Cranial Irradiation. in Cellular and Molecular Neurobiology, 32(7), 129-1185.
https://hdl.handle.net/21.15107/rcub_ibiss_1104

Veličković N, Drakulić DR, Petrović SB, Grković IS, Milosević MS, Stanojlović, Milos  R, Horvat AI. Time-Course of Hypothalamic-Pituitary-Adrenal Axis Activity and Inflammation in Juvenile Rat Brain After Cranial Irradiation. in Cellular and Molecular Neurobiology. 2012;32(7):129-1185.
https://hdl.handle.net/21.15107/rcub_ibiss_1104 .

Veličković, Nataša, Drakulić, Dunja R, Petrović, Snjezana B, Grković, Ivana S, Milosević, Maja S, Stanojlović, Milos  R, Horvat, Anica I, "Time-Course of Hypothalamic-Pituitary-Adrenal Axis Activity and Inflammation in Juvenile Rat Brain After Cranial Irradiation" in Cellular and Molecular Neurobiology, 32, no. 7 (2012):129-1185,
https://hdl.handle.net/21.15107/rcub_ibiss_1104 .

TY  - JOUR
AU  - Milosević, Maja S
AU  - Petrović, Snjezana B
AU  - Veličković, Nataša
AU  - Grković, Ivana S
AU  - Ignjatović, Marija
AU  - Horvat, Anica I
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1084
AB  - Extracellular nucleotides affect female reproductive functions, fertilization, and pregnancy. The aim of this study was to investigate biochemical characteristics of ATP and ADP hydrolysis and identify E-NTPDases in myometrial cell membranes from Wistar albino rats. The apparent K (m) values were 506.4 +/- A 62.1 and 638.8 +/- A 31.3 mu M, with a calculated V (max) (app) of 3,973.0 +/- A 279.5 and 2,853.9 +/- A 79.8 nmol/min/mg for ATP and ADP, respectively. The enzyme activity described here has common properties characteristic for NTPDases: divalent cation dependence; alkaline pH optimum for both substrates, insensitivity to some of classical ATPase inhibitors (ouabain, oligomycine, theophylline, levamisole) and significant inhibition by suramine and high concentration of sodium azides (5 mM). According to similar apparent K-m values for both substrates, the ATP/ADP hydrolysis ratio, and Chevillard competition plot, NTPDase1 is dominant ATP/ADP hydrolyzing enzyme in myometrial cell membranes. RT-PCR analysis revealed expression of three members of ectonucleoside triphosphate diphosphohydrolase family (NTPDase 1, 2, and 8) in rat uterus. These findings may further elucidate the role of NTPDases and ATP in reproductive physiology.
T2  - Molecular and Cellular Biochemistry
T1  - ATP and ADP hydrolysis in cell membranes from rat myometrium
IS  - 1-2
VL  - 371
SP  - 248
EP  - 208
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1084
ER  - 

@article{
author = "Milosević, Maja S and Petrović, Snjezana B and Veličković, Nataša and Grković, Ivana S and Ignjatović, Marija and Horvat, Anica I",
year = "2012",
abstract = "Extracellular nucleotides affect female reproductive functions, fertilization, and pregnancy. The aim of this study was to investigate biochemical characteristics of ATP and ADP hydrolysis and identify E-NTPDases in myometrial cell membranes from Wistar albino rats. The apparent K (m) values were 506.4 +/- A 62.1 and 638.8 +/- A 31.3 mu M, with a calculated V (max) (app) of 3,973.0 +/- A 279.5 and 2,853.9 +/- A 79.8 nmol/min/mg for ATP and ADP, respectively. The enzyme activity described here has common properties characteristic for NTPDases: divalent cation dependence; alkaline pH optimum for both substrates, insensitivity to some of classical ATPase inhibitors (ouabain, oligomycine, theophylline, levamisole) and significant inhibition by suramine and high concentration of sodium azides (5 mM). According to similar apparent K-m values for both substrates, the ATP/ADP hydrolysis ratio, and Chevillard competition plot, NTPDase1 is dominant ATP/ADP hydrolyzing enzyme in myometrial cell membranes. RT-PCR analysis revealed expression of three members of ectonucleoside triphosphate diphosphohydrolase family (NTPDase 1, 2, and 8) in rat uterus. These findings may further elucidate the role of NTPDases and ATP in reproductive physiology.",
journal = "Molecular and Cellular Biochemistry",
title = "ATP and ADP hydrolysis in cell membranes from rat myometrium",
number = "1-2",
volume = "371",
pages = "248-208",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1084"
}

Milosević, M. S., Petrović, S. B., Veličković, N., Grković, I. S., Ignjatović, M.,& Horvat, A. I.. (2012). ATP and ADP hydrolysis in cell membranes from rat myometrium. in Molecular and Cellular Biochemistry, 371(1-2), 248-208.
https://hdl.handle.net/21.15107/rcub_ibiss_1084

Milosević MS, Petrović SB, Veličković N, Grković IS, Ignjatović M, Horvat AI. ATP and ADP hydrolysis in cell membranes from rat myometrium. in Molecular and Cellular Biochemistry. 2012;371(1-2):248-208.
https://hdl.handle.net/21.15107/rcub_ibiss_1084 .

Milosević, Maja S, Petrović, Snjezana B, Veličković, Nataša, Grković, Ivana S, Ignjatović, Marija, Horvat, Anica I, "ATP and ADP hydrolysis in cell membranes from rat myometrium" in Molecular and Cellular Biochemistry, 371, no. 1-2 (2012):248-208,
https://hdl.handle.net/21.15107/rcub_ibiss_1084 .