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  - Tatalović, Nikola
AU  - Veljković, Filip
AU  - Martinović, Jelena
AU  - Zarić Kontić, Marina
AU  - Blagojević, Duško
AU  - Stojanović, Zoran
AU  - Drakulić, Dunja
PY  - 2022
UR  - https://www.ecnp.eu/congress2022/ECNPcongress/programme/programme#!abstractdetails/0000506150
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5315
AB  - Introduction: Cerebral hypoperfusion (CH), a reduced cerebral blood flow, characteristic for aging and neurodegenerative disorders, might be associated with a pro-oxidative state in the brain due to the generation of reactive oxygen species (ROS) that cause neuronal damage. These overgenerated pro-oxidants might be reduced, disabled and neutralized by the endogenous antioxidant enzymes, including superoxide dismutase (SOD) and catalase (CAT). A sex steroid hormone, progesterone, in several experimental models of neuronal injury exerts anti-oxidative properties upregulating anti-oxidative molecules and thus promoting neuroprotection. However, its efficacy in the state of CH is still unknown and it is necessary to better understand the mechanism underlying this hormone’s neuroprotective effects.
Aim: We investigated whether progesterone is able to modulate CH-induced pro-oxidative/anti-oxidative imbalance, as well as SOD and CAT activities, in the prefrontal cortex of three-month-old male Wistar rats subjected to permanent bilateral common carotid artery occlusion (2VO).
Methods: The appropriate actions were undertaken to reduce the distress of the animals in agreement with the European Community Council Directive of 86/609/EEC and 010/63/EU for animal experiments. All experimental procedures were allowed by the Ethical Committee for the Use of Laboratory Animals of VINČA Institute of Nuclear Sciences - National Institute of thе Republic of Serbia, University of Belgrade, Belgrade, Republic of Serbia (protocol authorization numbers 02/11 and 323-07-04253/2016-05). Following chloral hydrate anaesthesia, 8 rats randomly assigned in 2VO groups were double occluded with 5–0 silk suture, while 4 animals from sham operated group were subjected to the same surgical procedure but without actual ligation of carotid arteries. Four hours following the surgical procedure animals from sham operated group, used as controls, were subcutaneously treated with vehicle (commercial flax oil, 1 mg/kg/day, S + V), while animals in 2VO groups were subjected to either progesterone (1.7 mg/kg/day, 2VO + P) or vehicle (commercial flax oil, 1 mg/kg/day, 2VO + V). Following 7 days lasting treatments, pro-oxidative/anti-oxidative balance was assessed according to the method of Alamdari et al. [1]; while activities of anti-oxidative enzymes were determined as described in the study by Tatalović et al. [2]. One-way analysis of variance (ANOVA) test followed by Tukey’s post hoc test was employed to analyse data. The values of p < 0.05 or less were considered statistically significant.
Results: Obtained results demonstrate that compared to controls, 2VO and vehicle treatment induced a significant increase of pro-oxidants levels (p < 0.01) as well as the activities of both investigated anti-oxidative enzymes, although only the CAT activity was significantly increased (p < 0.05). Following progesterone treatment, pro-oxidants levels were lowered to the control level which caused the difference between the 2VO groups (p < 0.05). In parallel, no statistically significant change in SOD activity was observed, while CAT was upregulated (p < 0.05).
Conclusion: Presented results suggest that in the prefrontal cortex in the state of CH, progesterone, by modulating the CAT activity, downregulates overgenerated reactive species, reduces CH-induced oxidative stress and exerts anti-oxidative outcomes.
The Ministry of Education, Science and Technological Development


Disclosure statement: Financially supported by The Ministry of Education, Science and Technological Development, grants No 451-03-1/2022-14/13 and 451-03-68/2022-14/ 200007 and 13451-03-68/2022-14/ 200175




 
[1] Alamdari, D.H., Ghayour-Mobarhan, M., Tavallaie, S., Parizadeh, M.R., Moohebati, M., Ghafoori, F., et al., 2008. Prooxidant–antioxidant balance as a new risk factor in patients with angiographically defined coronary artery disease. Clinical Biochemistry 41(6),375–380. 
[2] Tatalović, N., Vidonja Uzelac, T., Oreščanin Dušić, Z., Nikolić-Kokić, A., Bresjanac, M., Blagojević, D., 2021. Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and KATP Channels Mediated. Antioxidants 10(11),1792.
PB  - European College of Neuropsychopharmacology (ECNP)
C3  - The 35th ECNP Congress; 2023 Oct 7-10; Barcelona, Spain
T1  - Progesterone exerts protective effects in rat permanent bilateral common carotid artery occlusion model
IS  - P.0477
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5315
ER  - 

@conference{
author = "Guševac Stojanović, Ivana and Tatalović, Nikola and Veljković, Filip and Martinović, Jelena and Zarić Kontić, Marina and Blagojević, Duško and Stojanović, Zoran and Drakulić, Dunja",
year = "2022",
abstract = "Introduction: Cerebral hypoperfusion (CH), a reduced cerebral blood flow, characteristic for aging and neurodegenerative disorders, might be associated with a pro-oxidative state in the brain due to the generation of reactive oxygen species (ROS) that cause neuronal damage. These overgenerated pro-oxidants might be reduced, disabled and neutralized by the endogenous antioxidant enzymes, including superoxide dismutase (SOD) and catalase (CAT). A sex steroid hormone, progesterone, in several experimental models of neuronal injury exerts anti-oxidative properties upregulating anti-oxidative molecules and thus promoting neuroprotection. However, its efficacy in the state of CH is still unknown and it is necessary to better understand the mechanism underlying this hormone’s neuroprotective effects.
Aim: We investigated whether progesterone is able to modulate CH-induced pro-oxidative/anti-oxidative imbalance, as well as SOD and CAT activities, in the prefrontal cortex of three-month-old male Wistar rats subjected to permanent bilateral common carotid artery occlusion (2VO).
Methods: The appropriate actions were undertaken to reduce the distress of the animals in agreement with the European Community Council Directive of 86/609/EEC and 010/63/EU for animal experiments. All experimental procedures were allowed by the Ethical Committee for the Use of Laboratory Animals of VINČA Institute of Nuclear Sciences - National Institute of thе Republic of Serbia, University of Belgrade, Belgrade, Republic of Serbia (protocol authorization numbers 02/11 and 323-07-04253/2016-05). Following chloral hydrate anaesthesia, 8 rats randomly assigned in 2VO groups were double occluded with 5–0 silk suture, while 4 animals from sham operated group were subjected to the same surgical procedure but without actual ligation of carotid arteries. Four hours following the surgical procedure animals from sham operated group, used as controls, were subcutaneously treated with vehicle (commercial flax oil, 1 mg/kg/day, S + V), while animals in 2VO groups were subjected to either progesterone (1.7 mg/kg/day, 2VO + P) or vehicle (commercial flax oil, 1 mg/kg/day, 2VO + V). Following 7 days lasting treatments, pro-oxidative/anti-oxidative balance was assessed according to the method of Alamdari et al. [1]; while activities of anti-oxidative enzymes were determined as described in the study by Tatalović et al. [2]. One-way analysis of variance (ANOVA) test followed by Tukey’s post hoc test was employed to analyse data. The values of p < 0.05 or less were considered statistically significant.
Results: Obtained results demonstrate that compared to controls, 2VO and vehicle treatment induced a significant increase of pro-oxidants levels (p < 0.01) as well as the activities of both investigated anti-oxidative enzymes, although only the CAT activity was significantly increased (p < 0.05). Following progesterone treatment, pro-oxidants levels were lowered to the control level which caused the difference between the 2VO groups (p < 0.05). In parallel, no statistically significant change in SOD activity was observed, while CAT was upregulated (p < 0.05).
Conclusion: Presented results suggest that in the prefrontal cortex in the state of CH, progesterone, by modulating the CAT activity, downregulates overgenerated reactive species, reduces CH-induced oxidative stress and exerts anti-oxidative outcomes.
The Ministry of Education, Science and Technological Development


Disclosure statement: Financially supported by The Ministry of Education, Science and Technological Development, grants No 451-03-1/2022-14/13 and 451-03-68/2022-14/ 200007 and 13451-03-68/2022-14/ 200175




 
[1] Alamdari, D.H., Ghayour-Mobarhan, M., Tavallaie, S., Parizadeh, M.R., Moohebati, M., Ghafoori, F., et al., 2008. Prooxidant–antioxidant balance as a new risk factor in patients with angiographically defined coronary artery disease. Clinical Biochemistry 41(6),375–380. 
[2] Tatalović, N., Vidonja Uzelac, T., Oreščanin Dušić, Z., Nikolić-Kokić, A., Bresjanac, M., Blagojević, D., 2021. Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and KATP Channels Mediated. Antioxidants 10(11),1792.",
publisher = "European College of Neuropsychopharmacology (ECNP)",
journal = "The 35th ECNP Congress; 2023 Oct 7-10; Barcelona, Spain",
title = "Progesterone exerts protective effects in rat permanent bilateral common carotid artery occlusion model",
number = "P.0477",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5315"
}

Guševac Stojanović, I., Tatalović, N., Veljković, F., Martinović, J., Zarić Kontić, M., Blagojević, D., Stojanović, Z.,& Drakulić, D.. (2022). Progesterone exerts protective effects in rat permanent bilateral common carotid artery occlusion model. in The 35th ECNP Congress; 2023 Oct 7-10; Barcelona, Spain
European College of Neuropsychopharmacology (ECNP).(P.0477).
https://hdl.handle.net/21.15107/rcub_ibiss_5315

Guševac Stojanović I, Tatalović N, Veljković F, Martinović J, Zarić Kontić M, Blagojević D, Stojanović Z, Drakulić D. Progesterone exerts protective effects in rat permanent bilateral common carotid artery occlusion model. in The 35th ECNP Congress; 2023 Oct 7-10; Barcelona, Spain. 2022;(P.0477).
https://hdl.handle.net/21.15107/rcub_ibiss_5315 .

Guševac Stojanović, Ivana, Tatalović, Nikola, Veljković, Filip, Martinović, Jelena, Zarić Kontić, Marina, Blagojević, Duško, Stojanović, Zoran, Drakulić, Dunja, "Progesterone exerts protective effects in rat permanent bilateral common carotid artery occlusion model" in The 35th ECNP Congress; 2023 Oct 7-10; Barcelona, Spain, no. P.0477 (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5315 .