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  - Božić, Iva
AU  - Milošević, Katarina
AU  - Laketa, Danijela
AU  - Adžić, Marija
AU  - Jakovljević, Marija
AU  - Bjelobaba, Ivana
AU  - Savić, Danijela
AU  - Nedeljković, Nadežda
AU  - Peković, Sanja
AU  - Lavrnja, Irena
PY  - 2018
UR  - http://link.springer.com/10.1007/s11064-018-2509-8
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3027
AB  - Kv1.3 is a voltage gated potassium channel that has been implicated in pathophysiology of multiple sclerosis (MS). In the present study we investigated temporal and cellular expression pattern of this channel in the lumbar part of spinal cords of animals with experimental autoimmune encephalomyelitis (EAE), animal model of MS. EAE was actively induced in female Dark Agouti rats. Expression of Kv1.3 was analyzed at different time points of disease progression, at the onset, peak and end of EAE. We here show that Kv1.3 increased by several folds at the peak of EAE at both gene and protein level. Double immunofluorescence analyses demonstrated localization of Kv1.3 on activated microglia, macrophages, and reactive astrocytes around inflammatory lesions. In vitro experiments showed that pharmacological block of Kv1.3 in activated astrocytes suppresses the expression of proinflammatory mediators, suggesting a role of this channel in inflammation. Our results support the hypothesis that Kv1.3 may be a therapeutic target of interest for MS and add astrocytes to the list of cells whose activation would be suppressed by inhibiting Kv1.3 in inflammatory conditions.
T2  - Neurochemical Research
T1  - Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis.
IS  - 5
VL  - 43
DO  - 10.1007/s11064-018-2509-8
SP  - 1020
EP  - 1034
ER  - 

@article{
author = "Božić, Iva and Milošević, Katarina and Laketa, Danijela and Adžić, Marija and Jakovljević, Marija and Bjelobaba, Ivana and Savić, Danijela and Nedeljković, Nadežda and Peković, Sanja and Lavrnja, Irena",
year = "2018",
abstract = "Kv1.3 is a voltage gated potassium channel that has been implicated in pathophysiology of multiple sclerosis (MS). In the present study we investigated temporal and cellular expression pattern of this channel in the lumbar part of spinal cords of animals with experimental autoimmune encephalomyelitis (EAE), animal model of MS. EAE was actively induced in female Dark Agouti rats. Expression of Kv1.3 was analyzed at different time points of disease progression, at the onset, peak and end of EAE. We here show that Kv1.3 increased by several folds at the peak of EAE at both gene and protein level. Double immunofluorescence analyses demonstrated localization of Kv1.3 on activated microglia, macrophages, and reactive astrocytes around inflammatory lesions. In vitro experiments showed that pharmacological block of Kv1.3 in activated astrocytes suppresses the expression of proinflammatory mediators, suggesting a role of this channel in inflammation. Our results support the hypothesis that Kv1.3 may be a therapeutic target of interest for MS and add astrocytes to the list of cells whose activation would be suppressed by inhibiting Kv1.3 in inflammatory conditions.",
journal = "Neurochemical Research",
title = "Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis.",
number = "5",
volume = "43",
doi = "10.1007/s11064-018-2509-8",
pages = "1020-1034"
}

Božić, I., Milošević, K., Laketa, D., Adžić, M., Jakovljević, M., Bjelobaba, I., Savić, D., Nedeljković, N., Peković, S.,& Lavrnja, I.. (2018). Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis.. in Neurochemical Research, 43(5), 1020-1034.
https://doi.org/10.1007/s11064-018-2509-8

Božić I, Milošević K, Laketa D, Adžić M, Jakovljević M, Bjelobaba I, Savić D, Nedeljković N, Peković S, Lavrnja I. Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis.. in Neurochemical Research. 2018;43(5):1020-1034.
doi:10.1007/s11064-018-2509-8 .

Božić, Iva, Milošević, Katarina, Laketa, Danijela, Adžić, Marija, Jakovljević, Marija, Bjelobaba, Ivana, Savić, Danijela, Nedeljković, Nadežda, Peković, Sanja, Lavrnja, Irena, "Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis." in Neurochemical Research, 43, no. 5 (2018):1020-1034,
https://doi.org/10.1007/s11064-018-2509-8 . .

TY  - CONF
AU  - Jakovljević, Marija
AU  - Lavrnja, Irena
AU  - Božić, Iva
AU  - Adžić, Marija
AU  - Bjelobaba, Ivana
AU  - Savić, Danijela
AU  - Peković, Sanja
AU  - Nedeljković, Nadežda
AU  - Laketa, Danijela
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5985
AB  - Introduction. Multiple sclerosis (MS) is a chronic disease of central nervous system (CNS), characterized by neuroinflammation, demyelination and neurodegeneration. Despite well-established role of purinergic signaling in MS pathology, the role of ADP as ectonucleotidase inter-product between proinflammatory ATP and anti-inflammatory adenosine is still obscure. Among ADP-sensitive receptors P2Y1, P2Y12 and P2Y13, there are few data indicating involvement of P2Y12 receptor in MS. The aim of this study was to elucidate a potential impact of ADP on CNS pathology in animal model of MS - experimental autoimmune encephalomyelitis (EAE). Material and Methods. EAE was induced in 8-week old female rats of Dark Agouti strain. The abundance and localization of ADP receptors – P2Y1, P2Y12 and P2Y13 was analyzed in lumbosacral spinal cord tissue by real-time PCR, Western Blot and immunohistochemistry at different disease stages – onset (Eo), peak (Ep) and recovery (Er). Results. Results of this study show that ADP-sensing purinergic receptors are differentially regulated during EAE. Namely, mRNA and protein expression of P2Y1 and P2Y12was decreased at Eo, while significantly increased for P2Y12and P2Y13 at Ep and/or Er. In addition, immunohistochemical labeling showed similar pattern of changes during EAE for investigated receptors, thus providing novel insight into their spinal cord tissue distribution. Conclusion. Our results strongly indicate involvement of ADP-sensitive purinergic receptors P2Y1, P2Y12 and P2Y13 in pathophysiology of EAE. Their differential regulation and tissue distribution implies diverse effects in the course of the disease during EAE. Further studies would be necessary to elucidate their mechanisms of action.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia
T1  - ADP receptors P2Y1, P2Y12 and P2Y13 are differentially regulated in a rat model of multiple sclerosis
SP  - 68
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5985
ER  - 

@conference{
author = "Jakovljević, Marija and Lavrnja, Irena and Božić, Iva and Adžić, Marija and Bjelobaba, Ivana and Savić, Danijela and Peković, Sanja and Nedeljković, Nadežda and Laketa, Danijela",
year = "2017",
abstract = "Introduction. Multiple sclerosis (MS) is a chronic disease of central nervous system (CNS), characterized by neuroinflammation, demyelination and neurodegeneration. Despite well-established role of purinergic signaling in MS pathology, the role of ADP as ectonucleotidase inter-product between proinflammatory ATP and anti-inflammatory adenosine is still obscure. Among ADP-sensitive receptors P2Y1, P2Y12 and P2Y13, there are few data indicating involvement of P2Y12 receptor in MS. The aim of this study was to elucidate a potential impact of ADP on CNS pathology in animal model of MS - experimental autoimmune encephalomyelitis (EAE). Material and Methods. EAE was induced in 8-week old female rats of Dark Agouti strain. The abundance and localization of ADP receptors – P2Y1, P2Y12 and P2Y13 was analyzed in lumbosacral spinal cord tissue by real-time PCR, Western Blot and immunohistochemistry at different disease stages – onset (Eo), peak (Ep) and recovery (Er). Results. Results of this study show that ADP-sensing purinergic receptors are differentially regulated during EAE. Namely, mRNA and protein expression of P2Y1 and P2Y12was decreased at Eo, while significantly increased for P2Y12and P2Y13 at Ep and/or Er. In addition, immunohistochemical labeling showed similar pattern of changes during EAE for investigated receptors, thus providing novel insight into their spinal cord tissue distribution. Conclusion. Our results strongly indicate involvement of ADP-sensitive purinergic receptors P2Y1, P2Y12 and P2Y13 in pathophysiology of EAE. Their differential regulation and tissue distribution implies diverse effects in the course of the disease during EAE. Further studies would be necessary to elucidate their mechanisms of action.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia",
title = "ADP receptors P2Y1, P2Y12 and P2Y13 are differentially regulated in a rat model of multiple sclerosis",
pages = "68",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5985"
}

Jakovljević, M., Lavrnja, I., Božić, I., Adžić, M., Bjelobaba, I., Savić, D., Peković, S., Nedeljković, N.,& Laketa, D.. (2017). ADP receptors P2Y1, P2Y12 and P2Y13 are differentially regulated in a rat model of multiple sclerosis. in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 68.
https://hdl.handle.net/21.15107/rcub_ibiss_5985

Jakovljević M, Lavrnja I, Božić I, Adžić M, Bjelobaba I, Savić D, Peković S, Nedeljković N, Laketa D. ADP receptors P2Y1, P2Y12 and P2Y13 are differentially regulated in a rat model of multiple sclerosis. in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia. 2017;:68.
https://hdl.handle.net/21.15107/rcub_ibiss_5985 .

Jakovljević, Marija, Lavrnja, Irena, Božić, Iva, Adžić, Marija, Bjelobaba, Ivana, Savić, Danijela, Peković, Sanja, Nedeljković, Nadežda, Laketa, Danijela, "ADP receptors P2Y1, P2Y12 and P2Y13 are differentially regulated in a rat model of multiple sclerosis" in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia (2017):68,
https://hdl.handle.net/21.15107/rcub_ibiss_5985 .

TY  - JOUR
AU  - Adžić, Marija
AU  - Stevanović, Ivana
AU  - Josipović, Nataša
AU  - Laketa, Danijela
AU  - Lavrnja, Irena
AU  - Bjelobaba, Ivana
AU  - Božić, Iva
AU  - Jovanović, Marija
AU  - Milošević, Milena
AU  - Nedeljković, Nadežda
PY  - 2017
UR  - http://doi.wiley.com/10.1002/jnr.23950
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2560
AB  - It is widely accepted that adenosine triphosphate (ATP) acts as a universal danger-associated molecular pattern with several known mechanisms for immune cell activation. In the central nervous system, ATP activates microglia and astrocytes and induces a neuroinflammatory response. The aim of the present study was to describe responses of isolated astrocytes to increasing concentrations of ATP (5 µM to 1 mM), which were intended to mimic graded intensity of the extracellular stimulus. The results show that ATP induces graded activation response of astrocytes in terms of the cell proliferation, stellation, shape remodeling, and underlying actin and GFAP filament rearrangement, although the changes occurred without an apparent increase in GFAP and actin protein expression. On the other hand, ATP in the range of applied concentrations did not evoke IL-1β release from cultured astrocytes, nor did it modify the release from LPS and LPS+IFN-γ–primed astrocytes. ATP did not promote astrocyte migration in the wound-healing assay, nor did it increase production of reactive oxygen and nitrogen species and lipid peroxidation. Instead, ATP strengthened the antioxidative defense of astrocytes by inducing Cu/ZnSOD and MnSOD activities and by increasing their glutathione content. Our current results suggest that although ATP triggers several attributes of activated astrocytic phenotype with a magnitude that increases with the concentration, it is not sufficient to induce full-blown reactive phenotype of astrocytes in vitro. © 2016 Wiley Periodicals, Inc.
T2  - Journal of Neuroscience Research
T1  - Extracellular ATP induces graded reactive response of astrocytes and strengthens their antioxidative defense in vitro
IS  - 4
VL  - 95
DO  - 10.1002/jnr.23950
SP  - 1053
EP  - 1066
ER  - 

@article{
author = "Adžić, Marija and Stevanović, Ivana and Josipović, Nataša and Laketa, Danijela and Lavrnja, Irena and Bjelobaba, Ivana and Božić, Iva and Jovanović, Marija and Milošević, Milena and Nedeljković, Nadežda",
year = "2017",
abstract = "It is widely accepted that adenosine triphosphate (ATP) acts as a universal danger-associated molecular pattern with several known mechanisms for immune cell activation. In the central nervous system, ATP activates microglia and astrocytes and induces a neuroinflammatory response. The aim of the present study was to describe responses of isolated astrocytes to increasing concentrations of ATP (5 µM to 1 mM), which were intended to mimic graded intensity of the extracellular stimulus. The results show that ATP induces graded activation response of astrocytes in terms of the cell proliferation, stellation, shape remodeling, and underlying actin and GFAP filament rearrangement, although the changes occurred without an apparent increase in GFAP and actin protein expression. On the other hand, ATP in the range of applied concentrations did not evoke IL-1β release from cultured astrocytes, nor did it modify the release from LPS and LPS+IFN-γ–primed astrocytes. ATP did not promote astrocyte migration in the wound-healing assay, nor did it increase production of reactive oxygen and nitrogen species and lipid peroxidation. Instead, ATP strengthened the antioxidative defense of astrocytes by inducing Cu/ZnSOD and MnSOD activities and by increasing their glutathione content. Our current results suggest that although ATP triggers several attributes of activated astrocytic phenotype with a magnitude that increases with the concentration, it is not sufficient to induce full-blown reactive phenotype of astrocytes in vitro. © 2016 Wiley Periodicals, Inc.",
journal = "Journal of Neuroscience Research",
title = "Extracellular ATP induces graded reactive response of astrocytes and strengthens their antioxidative defense in vitro",
number = "4",
volume = "95",
doi = "10.1002/jnr.23950",
pages = "1053-1066"
}

Adžić, M., Stevanović, I., Josipović, N., Laketa, D., Lavrnja, I., Bjelobaba, I., Božić, I., Jovanović, M., Milošević, M.,& Nedeljković, N.. (2017). Extracellular ATP induces graded reactive response of astrocytes and strengthens their antioxidative defense in vitro. in Journal of Neuroscience Research, 95(4), 1053-1066.
https://doi.org/10.1002/jnr.23950

Adžić M, Stevanović I, Josipović N, Laketa D, Lavrnja I, Bjelobaba I, Božić I, Jovanović M, Milošević M, Nedeljković N. Extracellular ATP induces graded reactive response of astrocytes and strengthens their antioxidative defense in vitro. in Journal of Neuroscience Research. 2017;95(4):1053-1066.
doi:10.1002/jnr.23950 .

Adžić, Marija, Stevanović, Ivana, Josipović, Nataša, Laketa, Danijela, Lavrnja, Irena, Bjelobaba, Ivana, Božić, Iva, Jovanović, Marija, Milošević, Milena, Nedeljković, Nadežda, "Extracellular ATP induces graded reactive response of astrocytes and strengthens their antioxidative defense in vitro" in Journal of Neuroscience Research, 95, no. 4 (2017):1053-1066,
https://doi.org/10.1002/jnr.23950 . .