TY  - CONF
AU  - Dimitrijević, Dunja
AU  - Boranijašević, Sanja
AU  - Lavrnja, Irena
AU  - Adžić, Marija
AU  - Dragić, Milorad
AU  - Stekić, Anđela
AU  - Mihajlović, Katarina
AU  - Milenković, Ivan
AU  - Laketa, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5983
AB  - In preterm infants, insufficient exposure to endogenous glucocorticoids often leads to fatal complications. Therefore, synthetic glucocorticoids (sGC) are commonly applied to pregnant women at risk of preterm delivery between the 24th and 34th week of gestation. Despite the risk of adverse neurodevelopmental effects, repeat courses are frequently given. In the auditory system, the repeated sGC treatment prolonged neural transmission time and increased auditory thresholds in Wistar rats. Purinergic signaling plays an important role in the development of the auditory system.
We investigated the effects of repeated antenatal treatment with sGC on the components of the purinergic system in the developing auditory brainstem, at postnatal days (PD) 8,14, and 20 (pre-, post-hearing onset, and juvenile stage, respectively). Pregnant C57BL/6 dams received 0.4 mg/kg dexamethasone (DEX) s.c., at gestation days (GD) 15-17 (repeated course - 3DEX), mimicking clinical treatment for three consecutive weeks. In a single treatment (1 DEX), dams received DEX at GD 15, then saline at GD16 and 17. The control group (Sh) received saline. After treatment with 3DEX, a sharp decrease in immunoreactivity for A1 receptors and P2Y1 mRNA expression was observed (in PD8-20 and PD8, respectively). Although treatment effects were not detected for P2X2 receptor, we observed a developmental increase in its mRNA expression. P2X3 receptor, as well as CD73, CD39, and NTPDase2, exhibited stable expression.
In conclusion, repeated antenatal DEX treatment induced changes in A1 and P2Y1 receptors expression in the developing auditory brainstem, suggesting adverse neurodevelopmental effects, urging for evaluation of the current protocols for antenatal sGC treatment.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Developmental effects of repeated antenatal synthetic glucocorticoid treatment on purinergic signaling in the auditory brainstem
SP  - 64
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5983
ER  - 

@conference{
author = "Dimitrijević, Dunja and Boranijašević, Sanja and Lavrnja, Irena and Adžić, Marija and Dragić, Milorad and Stekić, Anđela and Mihajlović, Katarina and Milenković, Ivan and Laketa, Danijela",
year = "2023",
abstract = "In preterm infants, insufficient exposure to endogenous glucocorticoids often leads to fatal complications. Therefore, synthetic glucocorticoids (sGC) are commonly applied to pregnant women at risk of preterm delivery between the 24th and 34th week of gestation. Despite the risk of adverse neurodevelopmental effects, repeat courses are frequently given. In the auditory system, the repeated sGC treatment prolonged neural transmission time and increased auditory thresholds in Wistar rats. Purinergic signaling plays an important role in the development of the auditory system.
We investigated the effects of repeated antenatal treatment with sGC on the components of the purinergic system in the developing auditory brainstem, at postnatal days (PD) 8,14, and 20 (pre-, post-hearing onset, and juvenile stage, respectively). Pregnant C57BL/6 dams received 0.4 mg/kg dexamethasone (DEX) s.c., at gestation days (GD) 15-17 (repeated course - 3DEX), mimicking clinical treatment for three consecutive weeks. In a single treatment (1 DEX), dams received DEX at GD 15, then saline at GD16 and 17. The control group (Sh) received saline. After treatment with 3DEX, a sharp decrease in immunoreactivity for A1 receptors and P2Y1 mRNA expression was observed (in PD8-20 and PD8, respectively). Although treatment effects were not detected for P2X2 receptor, we observed a developmental increase in its mRNA expression. P2X3 receptor, as well as CD73, CD39, and NTPDase2, exhibited stable expression.
In conclusion, repeated antenatal DEX treatment induced changes in A1 and P2Y1 receptors expression in the developing auditory brainstem, suggesting adverse neurodevelopmental effects, urging for evaluation of the current protocols for antenatal sGC treatment.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Developmental effects of repeated antenatal synthetic glucocorticoid treatment on purinergic signaling in the auditory brainstem",
pages = "64",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5983"
}

Dimitrijević, D., Boranijašević, S., Lavrnja, I., Adžić, M., Dragić, M., Stekić, A., Mihajlović, K., Milenković, I.,& Laketa, D.. (2023). Developmental effects of repeated antenatal synthetic glucocorticoid treatment on purinergic signaling in the auditory brainstem. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 64.
https://hdl.handle.net/21.15107/rcub_ibiss_5983

Dimitrijević D, Boranijašević S, Lavrnja I, Adžić M, Dragić M, Stekić A, Mihajlović K, Milenković I, Laketa D. Developmental effects of repeated antenatal synthetic glucocorticoid treatment on purinergic signaling in the auditory brainstem. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:64.
https://hdl.handle.net/21.15107/rcub_ibiss_5983 .

Dimitrijević, Dunja, Boranijašević, Sanja, Lavrnja, Irena, Adžić, Marija, Dragić, Milorad, Stekić, Anđela, Mihajlović, Katarina, Milenković, Ivan, Laketa, Danijela, "Developmental effects of repeated antenatal synthetic glucocorticoid treatment on purinergic signaling in the auditory brainstem" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):64,
https://hdl.handle.net/21.15107/rcub_ibiss_5983 .

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  - JOUR
AU  - Dragić, Milorad
AU  - Zeljković, Milica
AU  - Stevanović, Ivana
AU  - Ilić, Tihomir
AU  - Ilić, Nela
AU  - Nedeljković, Nadezda
AU  - Ninković, Milica
PY  - 2020
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32599126
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3768
AB  - Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by inflammatory processes in the central nervous system (CNS). Decades of research led to discovery of several disease-modifying therapeutics strategies with moderate success. Experimental autoimmune encephalomyelitis (EAE) is currently the most commonly used experimental model for MS and for studying various therapeutic approaches. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neurostimulation technique with multiple beneficial effects on healthy as well as CNS with pathology. However, the molecular and cellular mechanisms of rTMS on acute EAE are scarce. Our study demonstrated beneficial effects of theta-burst stimulation (TBS), an experimental paradigm of rTMS, on disease course of acute EAE. TBS treatment attenuated reactive gliosis, restored myelin sheet and down-regulated expression of vimentin in EAE rats. These effects were reflected through reduced clinical parameters, shorter duration of illness and days spent in paralysis. Based on our research, rTMS deserves further considerations for its neuroprotective effect on EAE, and is an excellent candidate for further research and points that it could be used for more than for simple symptomatic therapy.
PB  - Elsevier BV
T2  - Brain Research Bulletin
T1  - Theta burst stimulation ameliorates symptoms of experimental autoimmune encephalomyelitis and attenuates reactive gliosis.
VL  - 162
DO  - 10.1016/j.brainresbull.2020.06.013
SP  - 208
EP  - 217
ER  - 

@article{
author = "Dragić, Milorad and Zeljković, Milica and Stevanović, Ivana and Ilić, Tihomir and Ilić, Nela and Nedeljković, Nadezda and Ninković, Milica",
year = "2020",
abstract = "Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by inflammatory processes in the central nervous system (CNS). Decades of research led to discovery of several disease-modifying therapeutics strategies with moderate success. Experimental autoimmune encephalomyelitis (EAE) is currently the most commonly used experimental model for MS and for studying various therapeutic approaches. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neurostimulation technique with multiple beneficial effects on healthy as well as CNS with pathology. However, the molecular and cellular mechanisms of rTMS on acute EAE are scarce. Our study demonstrated beneficial effects of theta-burst stimulation (TBS), an experimental paradigm of rTMS, on disease course of acute EAE. TBS treatment attenuated reactive gliosis, restored myelin sheet and down-regulated expression of vimentin in EAE rats. These effects were reflected through reduced clinical parameters, shorter duration of illness and days spent in paralysis. Based on our research, rTMS deserves further considerations for its neuroprotective effect on EAE, and is an excellent candidate for further research and points that it could be used for more than for simple symptomatic therapy.",
publisher = "Elsevier BV",
journal = "Brain Research Bulletin",
title = "Theta burst stimulation ameliorates symptoms of experimental autoimmune encephalomyelitis and attenuates reactive gliosis.",
volume = "162",
doi = "10.1016/j.brainresbull.2020.06.013",
pages = "208-217"
}

Dragić, M., Zeljković, M., Stevanović, I., Ilić, T., Ilić, N., Nedeljković, N.,& Ninković, M.. (2020). Theta burst stimulation ameliorates symptoms of experimental autoimmune encephalomyelitis and attenuates reactive gliosis.. in Brain Research Bulletin
Elsevier BV., 162, 208-217.
https://doi.org/10.1016/j.brainresbull.2020.06.013

Dragić M, Zeljković M, Stevanović I, Ilić T, Ilić N, Nedeljković N, Ninković M. Theta burst stimulation ameliorates symptoms of experimental autoimmune encephalomyelitis and attenuates reactive gliosis.. in Brain Research Bulletin. 2020;162:208-217.
doi:10.1016/j.brainresbull.2020.06.013 .

Dragić, Milorad, Zeljković, Milica, Stevanović, Ivana, Ilić, Tihomir, Ilić, Nela, Nedeljković, Nadezda, Ninković, Milica, "Theta burst stimulation ameliorates symptoms of experimental autoimmune encephalomyelitis and attenuates reactive gliosis." in Brain Research Bulletin, 162 (2020):208-217,
https://doi.org/10.1016/j.brainresbull.2020.06.013 . .