TY  - JOUR
AU  - Adžić Bukvić, Marija
AU  - Laketa, Danijela
AU  - Dragić, Milorad
AU  - Lavrnja, Irena
AU  - Nedeljković, Nadežda
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6368
AB  - Ecto-50-nucleotidase/CD73 (eN/CD73) is a membrane-bound enzyme involved in
extracellular production of adenosine and a cell adhesion molecule involved in cell–
cell interactions. In neuroinflammatory conditions such as experimental autoimmune
encephalomyelitis (EAE), reactive astrocytes occupying active demyelination areas
significantly upregulate eN/CD73 and express additional eN/CD73 variants. The present
study investigated whether the different eN/CD73 variants represent distinct
glycoforms and the functional consequences of their expression in neuroinflammatory
states. The study was performed in animals at different stages of EAE and in primary
astrocyte cultures treated with a range of inflammatory cytokines. Upregulation
at the mRNA, protein, and functional levels, as well as the appearance of multiple
eN/CD73 glycovariants were detected in the inflamed spinal cord tissue. At the peak
of the disease, eN/CD73 exhibited higher AMP turnover and lower enzymesubstrate
affinity than the control group, which was attributed to altered glycosylation
under neuroinflammatory conditions. A subsequent in vitro study showed that
primary astrocytes upregulated eN/CD73 and expressed the multiple glycovariants
upon stimulation with TNFα, IL-1β, IL-6, and ATP, with the effect occurring at least in
part via induction of JAK/STAT3 signaling. Experimental removal of glycan moieties
from membrane glycoproteins by PNGaseF decreased eN/CD73 activity but had no
effect on the enzyme's involvement in astrocyte migration. Our results suggest that
neuroinflammatory states are associated with the appearance of functionally distinct
eN/CD73 glycovariants, which may play a role in the development of the reactive
astrocyte phenotype.
PB  - Hoboken: Wiley
T2  - Glia
T1  - Expression of functionally distinct ecto-5'-nucleotidase/CD73 glycovariants in reactive astrocytes in experimental autoimmune encephalomyelitis and neuroinflammatory conditions in vitro
IS  - 1
VL  - 72
DO  - 10.1002/glia.24459
SP  - 19
EP  - 33
ER  - 

@article{
author = "Adžić Bukvić, Marija and Laketa, Danijela and Dragić, Milorad and Lavrnja, Irena and Nedeljković, Nadežda",
year = "2024",
abstract = "Ecto-50-nucleotidase/CD73 (eN/CD73) is a membrane-bound enzyme involved in
extracellular production of adenosine and a cell adhesion molecule involved in cell–
cell interactions. In neuroinflammatory conditions such as experimental autoimmune
encephalomyelitis (EAE), reactive astrocytes occupying active demyelination areas
significantly upregulate eN/CD73 and express additional eN/CD73 variants. The present
study investigated whether the different eN/CD73 variants represent distinct
glycoforms and the functional consequences of their expression in neuroinflammatory
states. The study was performed in animals at different stages of EAE and in primary
astrocyte cultures treated with a range of inflammatory cytokines. Upregulation
at the mRNA, protein, and functional levels, as well as the appearance of multiple
eN/CD73 glycovariants were detected in the inflamed spinal cord tissue. At the peak
of the disease, eN/CD73 exhibited higher AMP turnover and lower enzymesubstrate
affinity than the control group, which was attributed to altered glycosylation
under neuroinflammatory conditions. A subsequent in vitro study showed that
primary astrocytes upregulated eN/CD73 and expressed the multiple glycovariants
upon stimulation with TNFα, IL-1β, IL-6, and ATP, with the effect occurring at least in
part via induction of JAK/STAT3 signaling. Experimental removal of glycan moieties
from membrane glycoproteins by PNGaseF decreased eN/CD73 activity but had no
effect on the enzyme's involvement in astrocyte migration. Our results suggest that
neuroinflammatory states are associated with the appearance of functionally distinct
eN/CD73 glycovariants, which may play a role in the development of the reactive
astrocyte phenotype.",
publisher = "Hoboken: Wiley",
journal = "Glia",
title = "Expression of functionally distinct ecto-5'-nucleotidase/CD73 glycovariants in reactive astrocytes in experimental autoimmune encephalomyelitis and neuroinflammatory conditions in vitro",
number = "1",
volume = "72",
doi = "10.1002/glia.24459",
pages = "19-33"
}

Adžić Bukvić, M., Laketa, D., Dragić, M., Lavrnja, I.,& Nedeljković, N.. (2024). Expression of functionally distinct ecto-5'-nucleotidase/CD73 glycovariants in reactive astrocytes in experimental autoimmune encephalomyelitis and neuroinflammatory conditions in vitro. in Glia
Hoboken: Wiley., 72(1), 19-33.
https://doi.org/10.1002/glia.24459

Adžić Bukvić M, Laketa D, Dragić M, Lavrnja I, Nedeljković N. Expression of functionally distinct ecto-5'-nucleotidase/CD73 glycovariants in reactive astrocytes in experimental autoimmune encephalomyelitis and neuroinflammatory conditions in vitro. in Glia. 2024;72(1):19-33.
doi:10.1002/glia.24459 .

Adžić Bukvić, Marija, Laketa, Danijela, Dragić, Milorad, Lavrnja, Irena, Nedeljković, Nadežda, "Expression of functionally distinct ecto-5'-nucleotidase/CD73 glycovariants in reactive astrocytes in experimental autoimmune encephalomyelitis and neuroinflammatory conditions in vitro" in Glia, 72, no. 1 (2024):19-33,
https://doi.org/10.1002/glia.24459 . .

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  - Lavrnja, Irena
AU  - Laketa, Danijela
AU  - Savić, Danijela
AU  - Božić, Iva
AU  - Bjelobaba, Ivana
AU  - Peković, Sanja
AU  - Nedeljkovic, Nadezda
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1981
AB  - Ecto-5'-nucleotidase/cluster of differentiation 73 (CD73) (eN) is a
   70-kDa glycoprotein expressed in several different mammalian tissues and
   cell types. It is the rate-limiting enzyme of the purine catabolic
   pathway, which catalyzes the hydrolysis of AMP to produce adenosine with
   known anti-inflammatory and immunosuppressive actions. There is strong
   evidence for lymphocyte and endothelial cell eN having a role in
   experimental autoimmune encephalomyelitis (EAE), but the role of eN in
   cell types within the central nervous system is less clear. We have
   previously shown that eN activity significantly increased in the lumbar
   spinal cord during EAE. The present study is aimed to explore molecular
   pattern of the eN upregulation over the course of the disease and cell
   type(s) accountable for the induction. EAE was induced in Dark Agouti
   (DA) rats by immunization with the spinal cord tissue homogenate and
   adjuvant. Animals were sacrificed 8, 15, and 28 days following
   immunization (D8, D15, and D28), i.e., at time points which corresponded
   to the presymptomatic, symptomatic, and postsymptomatic phases of the
   disease, respectively. Significant increase in eN activity and its
   upregulation at the gene and the protein levels were demonstrated at D15
   and less prominently at D28 in comparison to control. Additionally,
   reactive astrocytes abundantly present in the lumbar spinal cord
   parenchyma were identified as principal cell type with significantly
   elevated eN expression. In all experimental groups, eN was expressed as
   a 71-kDa protein band of uniform abundance, whereas the overexpression
   of eN at D15 and D28 was associated with the expression of a second
   75-kDa eN variant. The possible outcome of eN upregulation during EAE as
   a part of protective astrocyte repertoire contributing to the resolution
   of the disease is discussed.
T2  - Journal of Molecular Neuroscience
T1  - Expression of a Second Ecto-5'-Nucleotidase Variant Besides the Usual
 Protein in Symptomatic Phase of Experimental Autoimmune
 Encephalomyelitis
IS  - 4
VL  - 55
DO  - 10.1007/s12031-014-0445-x
SP  - 898
EP  - 911
ER  - 

@article{
author = "Lavrnja, Irena and Laketa, Danijela and Savić, Danijela and Božić, Iva and Bjelobaba, Ivana and Peković, Sanja and Nedeljkovic, Nadezda",
year = "2015",
abstract = "Ecto-5'-nucleotidase/cluster of differentiation 73 (CD73) (eN) is a
   70-kDa glycoprotein expressed in several different mammalian tissues and
   cell types. It is the rate-limiting enzyme of the purine catabolic
   pathway, which catalyzes the hydrolysis of AMP to produce adenosine with
   known anti-inflammatory and immunosuppressive actions. There is strong
   evidence for lymphocyte and endothelial cell eN having a role in
   experimental autoimmune encephalomyelitis (EAE), but the role of eN in
   cell types within the central nervous system is less clear. We have
   previously shown that eN activity significantly increased in the lumbar
   spinal cord during EAE. The present study is aimed to explore molecular
   pattern of the eN upregulation over the course of the disease and cell
   type(s) accountable for the induction. EAE was induced in Dark Agouti
   (DA) rats by immunization with the spinal cord tissue homogenate and
   adjuvant. Animals were sacrificed 8, 15, and 28 days following
   immunization (D8, D15, and D28), i.e., at time points which corresponded
   to the presymptomatic, symptomatic, and postsymptomatic phases of the
   disease, respectively. Significant increase in eN activity and its
   upregulation at the gene and the protein levels were demonstrated at D15
   and less prominently at D28 in comparison to control. Additionally,
   reactive astrocytes abundantly present in the lumbar spinal cord
   parenchyma were identified as principal cell type with significantly
   elevated eN expression. In all experimental groups, eN was expressed as
   a 71-kDa protein band of uniform abundance, whereas the overexpression
   of eN at D15 and D28 was associated with the expression of a second
   75-kDa eN variant. The possible outcome of eN upregulation during EAE as
   a part of protective astrocyte repertoire contributing to the resolution
   of the disease is discussed.",
journal = "Journal of Molecular Neuroscience",
title = "Expression of a Second Ecto-5'-Nucleotidase Variant Besides the Usual
 Protein in Symptomatic Phase of Experimental Autoimmune
 Encephalomyelitis",
number = "4",
volume = "55",
doi = "10.1007/s12031-014-0445-x",
pages = "898-911"
}

Lavrnja, I., Laketa, D., Savić, D., Božić, I., Bjelobaba, I., Peković, S.,& Nedeljkovic, N.. (2015). Expression of a Second Ecto-5'-Nucleotidase Variant Besides the Usual
 Protein in Symptomatic Phase of Experimental Autoimmune
 Encephalomyelitis. in Journal of Molecular Neuroscience, 55(4), 898-911.
https://doi.org/10.1007/s12031-014-0445-x

Lavrnja I, Laketa D, Savić D, Božić I, Bjelobaba I, Peković S, Nedeljkovic N. Expression of a Second Ecto-5'-Nucleotidase Variant Besides the Usual
 Protein in Symptomatic Phase of Experimental Autoimmune
 Encephalomyelitis. in Journal of Molecular Neuroscience. 2015;55(4):898-911.
doi:10.1007/s12031-014-0445-x .

Lavrnja, Irena, Laketa, Danijela, Savić, Danijela, Božić, Iva, Bjelobaba, Ivana, Peković, Sanja, Nedeljkovic, Nadezda, "Expression of a Second Ecto-5'-Nucleotidase Variant Besides the Usual
 Protein in Symptomatic Phase of Experimental Autoimmune
 Encephalomyelitis" in Journal of Molecular Neuroscience, 55, no. 4 (2015):898-911,
https://doi.org/10.1007/s12031-014-0445-x . .

TY  - JOUR
AU  - Božić, Iva
AU  - Savić, Danijela
AU  - Laketa, Danijela
AU  - Bjelobaba, Ivana
AU  - Milenkovic, Ivan
AU  - Peković, Sanja
AU  - Nedeljkovic, Nadezda
AU  - Lavrnja, Irena
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2001
AB  - Microglial cells are resident immune cells of the central nervous system
   (CNS), recognized as key elements in the regulation of neural
   homeostasis and the response to injury and repair. As excessive
   activation of microglia may lead to neurodegeneration, therapeutic
   strategies targeting its inhibition were shown to improve treatment of
   most neurodegenerative diseases. Benfotiamine is a synthetic vitamin B1
   (thiamine) derivate exerting potentially anti-inflammatory effects.
   Despite the encouraging results regarding benfotiamine potential to
   alleviate diabetic microangiopathy, neuropathy and other oxidative
   stress-induced pathological conditions, its activities and cellular
   mechanisms during microglial activation have yet to be elucidated. In
   the present study, the anti-inflammatory effects of benfotiamine were
   investigated in lipopolysaccharide (LPS)-stimulated murine BV-2
   microglia. We determined that benfotiamine remodels activated microglia
   to acquire the shape that is characteristic of non-stimulated BV-2
   cells. In addition, benfotiamine significantly decreased production of
   pro-inflammatory mediators such as inducible form of nitric oxide
   synthase (iNOS) and NO; cyclooxygenase-2 (COX-2), heat-shock protein 70
   (Hsp70), tumor necrosis factor alpha a (TNF-alpha), interleukin-6
   (IL-6), whereas it increased anti-inflammatory interleukin-10 (IL-10)
   production in LPS stimulated BV-2 microglia. Moreover, benfotiamine
   suppressed the phosphorylation of extracellular signal-regulated kinases
   1/2 (ERK1/2), c-Jun N-terminal kinases (JNK) and protein kinase B
   Akt/PKB. Treatment with specific inhibitors revealed that
   benfotiamine-mediated suppression of NO production was via JNK1/2 and
   Akt pathway, while the cytokine suppression includes ERK1/2, JNK1/2 and
   Akt pathways. Finally, the potentially protective effect is mediated by
   the suppression of translocation of nuclear factor
   kappa-light-chain-enhancer of activated B cells (NF-kappa B) in the
   nucleus. Therefore, benfotiamine may have therapeutic potential for
   neurodegenerative diseases by inhibiting inflammatory mediators and
   enhancing anti-inflammatory factor production in activated microglia.
T2  - Plos One
T1  - Benfotiamine Attenuates Inflammatory Response in LPS Stimulated BV-2
 Microglia
IS  - e0118372
VL  - 10
DO  - 10.1371/journal.pone.0118372
ER  - 

@article{
author = "Božić, Iva and Savić, Danijela and Laketa, Danijela and Bjelobaba, Ivana and Milenkovic, Ivan and Peković, Sanja and Nedeljkovic, Nadezda and Lavrnja, Irena",
year = "2015",
abstract = "Microglial cells are resident immune cells of the central nervous system
   (CNS), recognized as key elements in the regulation of neural
   homeostasis and the response to injury and repair. As excessive
   activation of microglia may lead to neurodegeneration, therapeutic
   strategies targeting its inhibition were shown to improve treatment of
   most neurodegenerative diseases. Benfotiamine is a synthetic vitamin B1
   (thiamine) derivate exerting potentially anti-inflammatory effects.
   Despite the encouraging results regarding benfotiamine potential to
   alleviate diabetic microangiopathy, neuropathy and other oxidative
   stress-induced pathological conditions, its activities and cellular
   mechanisms during microglial activation have yet to be elucidated. In
   the present study, the anti-inflammatory effects of benfotiamine were
   investigated in lipopolysaccharide (LPS)-stimulated murine BV-2
   microglia. We determined that benfotiamine remodels activated microglia
   to acquire the shape that is characteristic of non-stimulated BV-2
   cells. In addition, benfotiamine significantly decreased production of
   pro-inflammatory mediators such as inducible form of nitric oxide
   synthase (iNOS) and NO; cyclooxygenase-2 (COX-2), heat-shock protein 70
   (Hsp70), tumor necrosis factor alpha a (TNF-alpha), interleukin-6
   (IL-6), whereas it increased anti-inflammatory interleukin-10 (IL-10)
   production in LPS stimulated BV-2 microglia. Moreover, benfotiamine
   suppressed the phosphorylation of extracellular signal-regulated kinases
   1/2 (ERK1/2), c-Jun N-terminal kinases (JNK) and protein kinase B
   Akt/PKB. Treatment with specific inhibitors revealed that
   benfotiamine-mediated suppression of NO production was via JNK1/2 and
   Akt pathway, while the cytokine suppression includes ERK1/2, JNK1/2 and
   Akt pathways. Finally, the potentially protective effect is mediated by
   the suppression of translocation of nuclear factor
   kappa-light-chain-enhancer of activated B cells (NF-kappa B) in the
   nucleus. Therefore, benfotiamine may have therapeutic potential for
   neurodegenerative diseases by inhibiting inflammatory mediators and
   enhancing anti-inflammatory factor production in activated microglia.",
journal = "Plos One",
title = "Benfotiamine Attenuates Inflammatory Response in LPS Stimulated BV-2
 Microglia",
number = "e0118372",
volume = "10",
doi = "10.1371/journal.pone.0118372"
}

Božić, I., Savić, D., Laketa, D., Bjelobaba, I., Milenkovic, I., Peković, S., Nedeljkovic, N.,& Lavrnja, I.. (2015). Benfotiamine Attenuates Inflammatory Response in LPS Stimulated BV-2
 Microglia. in Plos One, 10(e0118372).
https://doi.org/10.1371/journal.pone.0118372

Božić I, Savić D, Laketa D, Bjelobaba I, Milenkovic I, Peković S, Nedeljkovic N, Lavrnja I. Benfotiamine Attenuates Inflammatory Response in LPS Stimulated BV-2
 Microglia. in Plos One. 2015;10(e0118372).
doi:10.1371/journal.pone.0118372 .

Božić, Iva, Savić, Danijela, Laketa, Danijela, Bjelobaba, Ivana, Milenkovic, Ivan, Peković, Sanja, Nedeljkovic, Nadezda, Lavrnja, Irena, "Benfotiamine Attenuates Inflammatory Response in LPS Stimulated BV-2
 Microglia" in Plos One, 10, no. e0118372 (2015),
https://doi.org/10.1371/journal.pone.0118372 . .

TY  - JOUR
AU  - Božić, Iva
AU  - Savić, Danijela
AU  - Stevanovic, Ivana
AU  - Peković, Sanja
AU  - Nedeljkovic, Nadezda
AU  - Lavrnja, Irena
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2363
AB  - Chronic microglial activation and resulting sustained neuroinflammatory
   reaction are generally associated with neurodegeneration. Activated
   microglia acquires proinflammatory cellular profile that generates
   oxidative burst. Their persistent activation exacerbates inflammation,
   which damages healthy neurons via cytotoxic mediators, such as
   superoxide radical anion and nitric oxide. In our recent study, we have
   shown that benfotiamine (S-benzoylthiamine 0-monophosphate) possesses
   anti-inflammatory effects. Here, the effects of benfotiamine on the
   pro-oxidative component of activity of LPS-stimulated BV -2 cells were
   investigated. The activation of microglia was accompanied by
   upregulation of intracellular antioxidative defense, which was further
   promoted in the presence of benfotiamine. Namely, activated microglia
   exposed to non-cytotoxic doses of benfotiamine showed increased levels
   and activities of hydrogen peroxide- and superoxide removing enzymes
   catalase and glutathione system, and superoxide dismutase. In addition,
   benfotiamine showed the capacity to directly scavenge superoxide radical
   anion. As a consequence, benfotiamine suppressed the activation of
   microglia and provoked a decrease in NO and O-center dot(2)- production
   and lipid peroxidation. In conclusion, benfotiamine might silence
   pro-oxidative activity of microglia to alleviate/prevent oxidative
   damage of neighboring CNS cells.
T2  - Frontiers in Cellular Neuroscience
T1  - Benfotiamine upregulates antioxidative system in activated BV-2
 microglia cells
IS  - 351
VL  - 9
DO  - 10.3389/fncel.2015.00351
ER  - 

@article{
author = "Božić, Iva and Savić, Danijela and Stevanovic, Ivana and Peković, Sanja and Nedeljkovic, Nadezda and Lavrnja, Irena",
year = "2015",
abstract = "Chronic microglial activation and resulting sustained neuroinflammatory
   reaction are generally associated with neurodegeneration. Activated
   microglia acquires proinflammatory cellular profile that generates
   oxidative burst. Their persistent activation exacerbates inflammation,
   which damages healthy neurons via cytotoxic mediators, such as
   superoxide radical anion and nitric oxide. In our recent study, we have
   shown that benfotiamine (S-benzoylthiamine 0-monophosphate) possesses
   anti-inflammatory effects. Here, the effects of benfotiamine on the
   pro-oxidative component of activity of LPS-stimulated BV -2 cells were
   investigated. The activation of microglia was accompanied by
   upregulation of intracellular antioxidative defense, which was further
   promoted in the presence of benfotiamine. Namely, activated microglia
   exposed to non-cytotoxic doses of benfotiamine showed increased levels
   and activities of hydrogen peroxide- and superoxide removing enzymes
   catalase and glutathione system, and superoxide dismutase. In addition,
   benfotiamine showed the capacity to directly scavenge superoxide radical
   anion. As a consequence, benfotiamine suppressed the activation of
   microglia and provoked a decrease in NO and O-center dot(2)- production
   and lipid peroxidation. In conclusion, benfotiamine might silence
   pro-oxidative activity of microglia to alleviate/prevent oxidative
   damage of neighboring CNS cells.",
journal = "Frontiers in Cellular Neuroscience",
title = "Benfotiamine upregulates antioxidative system in activated BV-2
 microglia cells",
number = "351",
volume = "9",
doi = "10.3389/fncel.2015.00351"
}

Božić, I., Savić, D., Stevanovic, I., Peković, S., Nedeljkovic, N.,& Lavrnja, I.. (2015). Benfotiamine upregulates antioxidative system in activated BV-2
 microglia cells. in Frontiers in Cellular Neuroscience, 9(351).
https://doi.org/10.3389/fncel.2015.00351

Božić I, Savić D, Stevanovic I, Peković S, Nedeljkovic N, Lavrnja I. Benfotiamine upregulates antioxidative system in activated BV-2
 microglia cells. in Frontiers in Cellular Neuroscience. 2015;9(351).
doi:10.3389/fncel.2015.00351 .

Božić, Iva, Savić, Danijela, Stevanovic, Ivana, Peković, Sanja, Nedeljkovic, Nadezda, Lavrnja, Irena, "Benfotiamine upregulates antioxidative system in activated BV-2
 microglia cells" in Frontiers in Cellular Neuroscience, 9, no. 351 (2015),
https://doi.org/10.3389/fncel.2015.00351 . .

TY  - JOUR
AU  - Laketa, Danijela
AU  - Savić, Jasmina
AU  - Bjelobaba, Ivana
AU  - Lavrnja, Irena
AU  - Vasić, Vesna
AU  - Stojiljković, Mirjana
AU  - Nedeljković, Nadežda
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2093
AB  - Background: Cortical stab injury (CSI) induces changes in the activity,
   expression and cellular distribution of specific ectonucleotidases at
   the injury site. Also, several experimentally induced neuropathologies
   are associated with changes in soluble ectonucleotidase activities in
   the plasma and serum, whilst various insults to the brain alter purine
   compounds levels in cerebrospinal fluid, but also in serum, indicating
   that insults to the brain may induce alterations in nucleotides release
   and rate of their hydrolysis in the vascular system. Since adenine
   nucleotides and adenosine regulate diverse cellular functions in the
   vascular system, including vascular tone, platelet aggregation and
   inflammatory responses of lymphocytes and macrophages, alterations of
   ectonucleotidase activities in the vascular system may be relevant for
   the clinical outcome of the primary insult.
   Methods: We explored ectonucleotidase activities using specific enzyme
   assays and determined adenine nucleotides concentrations by the UPLC
   method in the rat serum after cortical stab injury.
   Results: At 4-h post-injury, ATP and AMP hydrolysis increased by about
   60\% and 40\%, respectively, while phosphodiesterase activity remained
   unchanged. Also, at 4-h postinjury a marked decrease in ATP
   concentration and more than 2-fold increase in AMP concentration were
   recorded.
   Conclusions: CSI induces rapid up-regulation of nucleotide catabolizing
   soluble ectonucleotidases in rat serum, which leads to the observed
   shift in serum nucleotide levels. The results obtained imply that
   ectonucleotidases and adenine nucleotides participate in the
   communication between the brain and the vascular system in physiological
   and pathological conditions and thereby may be involved in the
   development of various human neuropathologies.
T2  - Journal of Medical Biochemistry
T1  - BRAIN INJURY ALTERS ECTONUCLEOTIDASE ACTIVITIES AND ADENINE NUCLEOTIDE
 LEVELS IN RAT SERUM
IS  - 2
VL  - 34
DO  - 10.2478/jomb-2014-0025
SP  - 215
EP  - 222
ER  - 

@article{
author = "Laketa, Danijela and Savić, Jasmina and Bjelobaba, Ivana and Lavrnja, Irena and Vasić, Vesna and Stojiljković, Mirjana and Nedeljković, Nadežda",
year = "2015",
abstract = "Background: Cortical stab injury (CSI) induces changes in the activity,
   expression and cellular distribution of specific ectonucleotidases at
   the injury site. Also, several experimentally induced neuropathologies
   are associated with changes in soluble ectonucleotidase activities in
   the plasma and serum, whilst various insults to the brain alter purine
   compounds levels in cerebrospinal fluid, but also in serum, indicating
   that insults to the brain may induce alterations in nucleotides release
   and rate of their hydrolysis in the vascular system. Since adenine
   nucleotides and adenosine regulate diverse cellular functions in the
   vascular system, including vascular tone, platelet aggregation and
   inflammatory responses of lymphocytes and macrophages, alterations of
   ectonucleotidase activities in the vascular system may be relevant for
   the clinical outcome of the primary insult.
   Methods: We explored ectonucleotidase activities using specific enzyme
   assays and determined adenine nucleotides concentrations by the UPLC
   method in the rat serum after cortical stab injury.
   Results: At 4-h post-injury, ATP and AMP hydrolysis increased by about
   60\% and 40\%, respectively, while phosphodiesterase activity remained
   unchanged. Also, at 4-h postinjury a marked decrease in ATP
   concentration and more than 2-fold increase in AMP concentration were
   recorded.
   Conclusions: CSI induces rapid up-regulation of nucleotide catabolizing
   soluble ectonucleotidases in rat serum, which leads to the observed
   shift in serum nucleotide levels. The results obtained imply that
   ectonucleotidases and adenine nucleotides participate in the
   communication between the brain and the vascular system in physiological
   and pathological conditions and thereby may be involved in the
   development of various human neuropathologies.",
journal = "Journal of Medical Biochemistry",
title = "BRAIN INJURY ALTERS ECTONUCLEOTIDASE ACTIVITIES AND ADENINE NUCLEOTIDE
 LEVELS IN RAT SERUM",
number = "2",
volume = "34",
doi = "10.2478/jomb-2014-0025",
pages = "215-222"
}

Laketa, D., Savić, J., Bjelobaba, I., Lavrnja, I., Vasić, V., Stojiljković, M.,& Nedeljković, N.. (2015). BRAIN INJURY ALTERS ECTONUCLEOTIDASE ACTIVITIES AND ADENINE NUCLEOTIDE
 LEVELS IN RAT SERUM. in Journal of Medical Biochemistry, 34(2), 215-222.
https://doi.org/10.2478/jomb-2014-0025

Laketa D, Savić J, Bjelobaba I, Lavrnja I, Vasić V, Stojiljković M, Nedeljković N. BRAIN INJURY ALTERS ECTONUCLEOTIDASE ACTIVITIES AND ADENINE NUCLEOTIDE
 LEVELS IN RAT SERUM. in Journal of Medical Biochemistry. 2015;34(2):215-222.
doi:10.2478/jomb-2014-0025 .

Laketa, Danijela, Savić, Jasmina, Bjelobaba, Ivana, Lavrnja, Irena, Vasić, Vesna, Stojiljković, Mirjana, Nedeljković, Nadežda, "BRAIN INJURY ALTERS ECTONUCLEOTIDASE ACTIVITIES AND ADENINE NUCLEOTIDE
 LEVELS IN RAT SERUM" in Journal of Medical Biochemistry, 34, no. 2 (2015):215-222,
https://doi.org/10.2478/jomb-2014-0025 . .

TY  - JOUR
AU  - Božić, Iva
AU  - Savić, Danijela
AU  - Jovanović, Marija
AU  - Bjelobaba, Ivana
AU  - Laketa, Danijela
AU  - Nedeljković, Nadežda
AU  - Stojiljković, Mirjana
AU  - Peković, Sanja
AU  - Lavrnja, Irena
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2047
AB  - Microglia play a key role in defending central nervous system from
   various internal and external threats. However, their excessive and/or
   chronic activation is associated with deleterious effects in a variety
   of neurodegenerative diseases. Previously, we have shown that ribavirin
   when applied in clinically relevant dosage (10 mu M) modulates activated
   microglia in complex fashion inducing both anti-and proinflammatory
   effects, simultaneously causing cytotoxicity. Here, we examined
   potential of low-dose ribavirin (0.1 and 1 mu M) to modulate activated
   BV-2 microglia. Morphological and functional activation of BV-2 cells
   was achieved with lipopolysaccharide (LPS) stimulation. Our results
   demonstrated that low-dose ribavirin did not induce cell death, while 10
   mu M ribavirin promoted LPS induced apoptosis. We determined that 1 mu M
   ribavirin was equally efficient in deactivation of LPS induced
   morphological changes as 10 mu M ribavirin treatment. Ribavirin showed
   halfway success in reducing markers of functional activation of
   microglia. Namely, none of the doses had effect on LPS triggered
   production of proinflammatory cytokine tumor necrosis factor alpha. On
   the other hand, low-dose ribavirin proved its effectiveness in reduction
   of another inflammatory mediator, nitric oxide, by inhibiting inducible
   form of nitric oxide synthase. Our results imply that low-dose ribavirin
   may alleviate nitrosative stress during neuroinflammation.
T2  - Analytical Cellular Pathology
T1  - Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of
 BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase
IS  - 923614
DO  - 10.1155/2015/923614
ER  - 

@article{
author = "Božić, Iva and Savić, Danijela and Jovanović, Marija and Bjelobaba, Ivana and Laketa, Danijela and Nedeljković, Nadežda and Stojiljković, Mirjana and Peković, Sanja and Lavrnja, Irena",
year = "2015",
abstract = "Microglia play a key role in defending central nervous system from
   various internal and external threats. However, their excessive and/or
   chronic activation is associated with deleterious effects in a variety
   of neurodegenerative diseases. Previously, we have shown that ribavirin
   when applied in clinically relevant dosage (10 mu M) modulates activated
   microglia in complex fashion inducing both anti-and proinflammatory
   effects, simultaneously causing cytotoxicity. Here, we examined
   potential of low-dose ribavirin (0.1 and 1 mu M) to modulate activated
   BV-2 microglia. Morphological and functional activation of BV-2 cells
   was achieved with lipopolysaccharide (LPS) stimulation. Our results
   demonstrated that low-dose ribavirin did not induce cell death, while 10
   mu M ribavirin promoted LPS induced apoptosis. We determined that 1 mu M
   ribavirin was equally efficient in deactivation of LPS induced
   morphological changes as 10 mu M ribavirin treatment. Ribavirin showed
   halfway success in reducing markers of functional activation of
   microglia. Namely, none of the doses had effect on LPS triggered
   production of proinflammatory cytokine tumor necrosis factor alpha. On
   the other hand, low-dose ribavirin proved its effectiveness in reduction
   of another inflammatory mediator, nitric oxide, by inhibiting inducible
   form of nitric oxide synthase. Our results imply that low-dose ribavirin
   may alleviate nitrosative stress during neuroinflammation.",
journal = "Analytical Cellular Pathology",
title = "Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of
 BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase",
number = "923614",
doi = "10.1155/2015/923614"
}

Božić, I., Savić, D., Jovanović, M., Bjelobaba, I., Laketa, D., Nedeljković, N., Stojiljković, M., Peković, S.,& Lavrnja, I.. (2015). Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of
 BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase. in Analytical Cellular Pathology(923614).
https://doi.org/10.1155/2015/923614

Božić I, Savić D, Jovanović M, Bjelobaba I, Laketa D, Nedeljković N, Stojiljković M, Peković S, Lavrnja I. Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of
 BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase. in Analytical Cellular Pathology. 2015;(923614).
doi:10.1155/2015/923614 .

Božić, Iva, Savić, Danijela, Jovanović, Marija, Bjelobaba, Ivana, Laketa, Danijela, Nedeljković, Nadežda, Stojiljković, Mirjana, Peković, Sanja, Lavrnja, Irena, "Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of
 BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase" in Analytical Cellular Pathology, no. 923614 (2015),
https://doi.org/10.1155/2015/923614 . .

TY  - JOUR
AU  - Brisevac, Dusica
AU  - Adzic, Marija
AU  - Laketa, Danijela
AU  - Parabucki, Ana
AU  - Milosevic, Milena
AU  - Lavrnja, Irena
AU  - Bjelobaba, Ivana
AU  - Sevigny, Jean
AU  - Kipp, Markus
AU  - Nedeljkovic, Nadezda
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2349
AB  - Extracellular ATP (eATP) acts as a danger-associated molecular pattern
   which induces reactive response of astrocytes after brain insult,
   including morphological remodeling of astrocytes, proliferation,
   chemotaxis, and release of proinflammatory cytokines. The responses
   induced by eATP are under control of ecto-nucleotidases, which catalyze
   sequential hydrolysis of ATP to adenosine. In the mammalian brain,
   ecto-nucleotidases comprise three enzyme families: ecto-nucleoside
   triphosphate diphosphohydrolases 1-3 (NTPDase1-3), ecto-nucleotide
   pyrophosphatase/phospodiesterases 1-3 (NPP1-3), and ecto-5'-nucleotidase
   (eN), which crucially determine ATP/adenosine ratio in the pericellular
   milieu. Altered expression of ecto-nucleotidases has been demonstrated
   in several experimental models of human brain dysfunctions. In the
   present study, we have explored the pattern of NTPDase1-3, NPP1-3, and
   eN expression by cultured cortical astrocytes challenged with 1 mmol/L
   ATP (eATP). At the transcriptional level, eATP upregulated expression of
   NTPDase1, NTPDase2, NPP2, and eN, while, at translational and functional
   levels, these were paralleled only by the induction of NTPDase2 and eN.
   Additionally, eATP altered membrane topology of eN, from clusters
   localized in membrane domains to continuous distribution along the cell
   membrane. Our results suggest that eATP, by upregulating NTPDase2 and eN
   and altering the enzyme membrane topology, affects local kinetics of ATP
   metabolism and signal transduction that may have important roles in the
   process related to inflammation and reactive gliosis.
T2  - Journal of Molecular Neuroscience
T1  - Extracellular ATP Selectively Upregulates Ecto-Nucleoside Triphosphate
 Diphosphohydrolase 2 and Ecto-5'-Nucleotidase by Rat Cortical Astrocytes
 In Vitro
IS  - 3
VL  - 57
DO  - 10.1007/s12031-015-0601-y
SP  - 452
EP  - 462
ER  - 

@article{
author = "Brisevac, Dusica and Adzic, Marija and Laketa, Danijela and Parabucki, Ana and Milosevic, Milena and Lavrnja, Irena and Bjelobaba, Ivana and Sevigny, Jean and Kipp, Markus and Nedeljkovic, Nadezda",
year = "2015",
abstract = "Extracellular ATP (eATP) acts as a danger-associated molecular pattern
   which induces reactive response of astrocytes after brain insult,
   including morphological remodeling of astrocytes, proliferation,
   chemotaxis, and release of proinflammatory cytokines. The responses
   induced by eATP are under control of ecto-nucleotidases, which catalyze
   sequential hydrolysis of ATP to adenosine. In the mammalian brain,
   ecto-nucleotidases comprise three enzyme families: ecto-nucleoside
   triphosphate diphosphohydrolases 1-3 (NTPDase1-3), ecto-nucleotide
   pyrophosphatase/phospodiesterases 1-3 (NPP1-3), and ecto-5'-nucleotidase
   (eN), which crucially determine ATP/adenosine ratio in the pericellular
   milieu. Altered expression of ecto-nucleotidases has been demonstrated
   in several experimental models of human brain dysfunctions. In the
   present study, we have explored the pattern of NTPDase1-3, NPP1-3, and
   eN expression by cultured cortical astrocytes challenged with 1 mmol/L
   ATP (eATP). At the transcriptional level, eATP upregulated expression of
   NTPDase1, NTPDase2, NPP2, and eN, while, at translational and functional
   levels, these were paralleled only by the induction of NTPDase2 and eN.
   Additionally, eATP altered membrane topology of eN, from clusters
   localized in membrane domains to continuous distribution along the cell
   membrane. Our results suggest that eATP, by upregulating NTPDase2 and eN
   and altering the enzyme membrane topology, affects local kinetics of ATP
   metabolism and signal transduction that may have important roles in the
   process related to inflammation and reactive gliosis.",
journal = "Journal of Molecular Neuroscience",
title = "Extracellular ATP Selectively Upregulates Ecto-Nucleoside Triphosphate
 Diphosphohydrolase 2 and Ecto-5'-Nucleotidase by Rat Cortical Astrocytes
 In Vitro",
number = "3",
volume = "57",
doi = "10.1007/s12031-015-0601-y",
pages = "452-462"
}

Brisevac, D., Adzic, M., Laketa, D., Parabucki, A., Milosevic, M., Lavrnja, I., Bjelobaba, I., Sevigny, J., Kipp, M.,& Nedeljkovic, N.. (2015). Extracellular ATP Selectively Upregulates Ecto-Nucleoside Triphosphate
 Diphosphohydrolase 2 and Ecto-5'-Nucleotidase by Rat Cortical Astrocytes
 In Vitro. in Journal of Molecular Neuroscience, 57(3), 452-462.
https://doi.org/10.1007/s12031-015-0601-y

Brisevac D, Adzic M, Laketa D, Parabucki A, Milosevic M, Lavrnja I, Bjelobaba I, Sevigny J, Kipp M, Nedeljkovic N. Extracellular ATP Selectively Upregulates Ecto-Nucleoside Triphosphate
 Diphosphohydrolase 2 and Ecto-5'-Nucleotidase by Rat Cortical Astrocytes
 In Vitro. in Journal of Molecular Neuroscience. 2015;57(3):452-462.
doi:10.1007/s12031-015-0601-y .

Brisevac, Dusica, Adzic, Marija, Laketa, Danijela, Parabucki, Ana, Milosevic, Milena, Lavrnja, Irena, Bjelobaba, Ivana, Sevigny, Jean, Kipp, Markus, Nedeljkovic, Nadezda, "Extracellular ATP Selectively Upregulates Ecto-Nucleoside Triphosphate
 Diphosphohydrolase 2 and Ecto-5'-Nucleotidase by Rat Cortical Astrocytes
 In Vitro" in Journal of Molecular Neuroscience, 57, no. 3 (2015):452-462,
https://doi.org/10.1007/s12031-015-0601-y . .

TY  - JOUR
AU  - Drakulic, Dunja
AU  - Stanojlovic, Milos
AU  - Nedeljkovic, Nadezda
AU  - Grkovic, Ivana
AU  - Velickovic, Natasa
AU  - Gusevac, Ivana
AU  - Mitrovic, Natasa
AU  - Buzadzic, Ivana
AU  - Horvat, Anica
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1982
AB  - Although dexamethasone (DEX), a synthetic glucocorticoid receptor (GR)
   analog with profound effects on energy metabolism, immune system, and
   hypothalamic-pituitary-adrenal axis, is widely used therapeutically, its
   impact on the brain is poorly understood. The aim of the present study
   was to explore the effect of repeated low-dose DEX administration on the
   activity and expression of the ectonucleotidase enzymes which hydrolyze
   and therefore control extracellular ATP and adenosine concentrations in
   the synaptic cleft. Ectonucleotidases tested were ectonucleoside
   triphosphate diphosphohydrolase 1-3 (NTPDase1-3) and
   ecto-5'-nucleotidase (eN), whereas the effects were evaluated in two
   brain areas that show different sensitivity to glucocorticoid action,
   hippocampus, and cerebral cortex. In the hippocampus, but not in
   cerebral cortex, modest level of neurodegenerative changes as well as
   increase in ATP, ADP, and AMP hydrolysis and upregulation of NTPDase1
   and eN mRNA expression ensued under the influence of DEX. The observed
   pattern of ectonucleotidase activation, which creates tissue volume with
   enhanced capacity for adenosine formation, is the hallmark of the
   response after different insults to the brain.
T2  - Journal of Molecular Neuroscience
T1  - Upregulation of Nucleoside Triphosphate Diphosphohydrolase-1 and
 Ecto-5'-Nucleotidase in Rat Hippocampus after Repeated Low-Dose
 Dexamethasone Administration
IS  - 4
VL  - 55
DO  - 10.1007/s12031-014-0452-y
SP  - 959
EP  - 967
ER  - 

@article{
author = "Drakulic, Dunja and Stanojlovic, Milos and Nedeljkovic, Nadezda and Grkovic, Ivana and Velickovic, Natasa and Gusevac, Ivana and Mitrovic, Natasa and Buzadzic, Ivana and Horvat, Anica",
year = "2015",
abstract = "Although dexamethasone (DEX), a synthetic glucocorticoid receptor (GR)
   analog with profound effects on energy metabolism, immune system, and
   hypothalamic-pituitary-adrenal axis, is widely used therapeutically, its
   impact on the brain is poorly understood. The aim of the present study
   was to explore the effect of repeated low-dose DEX administration on the
   activity and expression of the ectonucleotidase enzymes which hydrolyze
   and therefore control extracellular ATP and adenosine concentrations in
   the synaptic cleft. Ectonucleotidases tested were ectonucleoside
   triphosphate diphosphohydrolase 1-3 (NTPDase1-3) and
   ecto-5'-nucleotidase (eN), whereas the effects were evaluated in two
   brain areas that show different sensitivity to glucocorticoid action,
   hippocampus, and cerebral cortex. In the hippocampus, but not in
   cerebral cortex, modest level of neurodegenerative changes as well as
   increase in ATP, ADP, and AMP hydrolysis and upregulation of NTPDase1
   and eN mRNA expression ensued under the influence of DEX. The observed
   pattern of ectonucleotidase activation, which creates tissue volume with
   enhanced capacity for adenosine formation, is the hallmark of the
   response after different insults to the brain.",
journal = "Journal of Molecular Neuroscience",
title = "Upregulation of Nucleoside Triphosphate Diphosphohydrolase-1 and
 Ecto-5'-Nucleotidase in Rat Hippocampus after Repeated Low-Dose
 Dexamethasone Administration",
number = "4",
volume = "55",
doi = "10.1007/s12031-014-0452-y",
pages = "959-967"
}

Drakulic, D., Stanojlovic, M., Nedeljkovic, N., Grkovic, I., Velickovic, N., Gusevac, I., Mitrovic, N., Buzadzic, I.,& Horvat, A.. (2015). Upregulation of Nucleoside Triphosphate Diphosphohydrolase-1 and
 Ecto-5'-Nucleotidase in Rat Hippocampus after Repeated Low-Dose
 Dexamethasone Administration. in Journal of Molecular Neuroscience, 55(4), 959-967.
https://doi.org/10.1007/s12031-014-0452-y

Drakulic D, Stanojlovic M, Nedeljkovic N, Grkovic I, Velickovic N, Gusevac I, Mitrovic N, Buzadzic I, Horvat A. Upregulation of Nucleoside Triphosphate Diphosphohydrolase-1 and
 Ecto-5'-Nucleotidase in Rat Hippocampus after Repeated Low-Dose
 Dexamethasone Administration. in Journal of Molecular Neuroscience. 2015;55(4):959-967.
doi:10.1007/s12031-014-0452-y .

Drakulic, Dunja, Stanojlovic, Milos, Nedeljkovic, Nadezda, Grkovic, Ivana, Velickovic, Natasa, Gusevac, Ivana, Mitrovic, Natasa, Buzadzic, Ivana, Horvat, Anica, "Upregulation of Nucleoside Triphosphate Diphosphohydrolase-1 and
 Ecto-5'-Nucleotidase in Rat Hippocampus after Repeated Low-Dose
 Dexamethasone Administration" in Journal of Molecular Neuroscience, 55, no. 4 (2015):959-967,
https://doi.org/10.1007/s12031-014-0452-y . .

TY  - JOUR
AU  - Grkovic, Ivana
AU  - Bjelobaba, Ivana
AU  - Nedeljkovic, Nadezda
AU  - Mitrovic, Natasa
AU  - Drakulic, Dunja
AU  - Stanojlovic, Milos
AU  - Horvat, Anica
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2170
AB  - Ecto-5'-nucleotidase (e-5NT), a glycosylphosphatidylinositol-linked
   membrane protein, catalyzes a conversion of AMP to adenosine, which
   influences nearly every aspect of brain physiology, including embryonic
   and postnatal brain development. The present study aimed to investigate
   a pattern of expression, activity and kinetic properties of e-5NT in the
   hippocampal formation and synaptic plasma membrane (SPM) preparations in
   rats at postnatal days (PDs) 7, 15, 20, 30 and 90. By combining gene
   expression analysis and enzyme histochemistry, we observed that e-5NT
   mRNA reached the adult level at PD20, while the enzyme activity
   continued to increase beyond this age. Further analysis revealed that
   hippocampal layers rich in synapses expressed the highest levels of
   e-5NT activity, while in layers populated with neuronal cell bodies, the
   enzyme activity was weak or absent. Therefore, activity and expression
   of e-5NT were analyzed in SPM preparations isolated from rats at
   different ages. The presence of two protein bands of about 65 and 68 kDa
   was determined by immunoblot analysis. The 65-kDa band was present at
   all ages, and its abundance increased from PD7 to PD20. The 68-kDa band
   appeared at PD15 and increased until PD30, coinciding with the increase
   of e-5NT activity, substrate affinity and enzymatic efficiency. Since
   distinct e-5NT isoforms may derive from different patterns of the enzyme
   protein N-glycosylation, we speculate that long-term regulation of e-5NT
   activity in adulthood may be effectuated at posttranslational level and
   without overall change in the gene and protein expression.
T2  - Journal of Molecular Neuroscience
T1  - Developmental Increase in Ecto-5'-Nucleotidase Activity Overlaps with
 Appearance of Two Immunologically Distinct Enzyme Isoforms in Rat
 Hippocampal Synaptic Plasma Membranes
IS  - 1
VL  - 54
DO  - 10.1007/s12031-014-0256-0
SP  - 109
EP  - 118
ER  - 

@article{
author = "Grkovic, Ivana and Bjelobaba, Ivana and Nedeljkovic, Nadezda and Mitrovic, Natasa and Drakulic, Dunja and Stanojlovic, Milos and Horvat, Anica",
year = "2014",
abstract = "Ecto-5'-nucleotidase (e-5NT), a glycosylphosphatidylinositol-linked
   membrane protein, catalyzes a conversion of AMP to adenosine, which
   influences nearly every aspect of brain physiology, including embryonic
   and postnatal brain development. The present study aimed to investigate
   a pattern of expression, activity and kinetic properties of e-5NT in the
   hippocampal formation and synaptic plasma membrane (SPM) preparations in
   rats at postnatal days (PDs) 7, 15, 20, 30 and 90. By combining gene
   expression analysis and enzyme histochemistry, we observed that e-5NT
   mRNA reached the adult level at PD20, while the enzyme activity
   continued to increase beyond this age. Further analysis revealed that
   hippocampal layers rich in synapses expressed the highest levels of
   e-5NT activity, while in layers populated with neuronal cell bodies, the
   enzyme activity was weak or absent. Therefore, activity and expression
   of e-5NT were analyzed in SPM preparations isolated from rats at
   different ages. The presence of two protein bands of about 65 and 68 kDa
   was determined by immunoblot analysis. The 65-kDa band was present at
   all ages, and its abundance increased from PD7 to PD20. The 68-kDa band
   appeared at PD15 and increased until PD30, coinciding with the increase
   of e-5NT activity, substrate affinity and enzymatic efficiency. Since
   distinct e-5NT isoforms may derive from different patterns of the enzyme
   protein N-glycosylation, we speculate that long-term regulation of e-5NT
   activity in adulthood may be effectuated at posttranslational level and
   without overall change in the gene and protein expression.",
journal = "Journal of Molecular Neuroscience",
title = "Developmental Increase in Ecto-5'-Nucleotidase Activity Overlaps with
 Appearance of Two Immunologically Distinct Enzyme Isoforms in Rat
 Hippocampal Synaptic Plasma Membranes",
number = "1",
volume = "54",
doi = "10.1007/s12031-014-0256-0",
pages = "109-118"
}

Grkovic, I., Bjelobaba, I., Nedeljkovic, N., Mitrovic, N., Drakulic, D., Stanojlovic, M.,& Horvat, A.. (2014). Developmental Increase in Ecto-5'-Nucleotidase Activity Overlaps with
 Appearance of Two Immunologically Distinct Enzyme Isoforms in Rat
 Hippocampal Synaptic Plasma Membranes. in Journal of Molecular Neuroscience, 54(1), 109-118.
https://doi.org/10.1007/s12031-014-0256-0

Grkovic I, Bjelobaba I, Nedeljkovic N, Mitrovic N, Drakulic D, Stanojlovic M, Horvat A. Developmental Increase in Ecto-5'-Nucleotidase Activity Overlaps with
 Appearance of Two Immunologically Distinct Enzyme Isoforms in Rat
 Hippocampal Synaptic Plasma Membranes. in Journal of Molecular Neuroscience. 2014;54(1):109-118.
doi:10.1007/s12031-014-0256-0 .

Grkovic, Ivana, Bjelobaba, Ivana, Nedeljkovic, Nadezda, Mitrovic, Natasa, Drakulic, Dunja, Stanojlovic, Milos, Horvat, Anica, "Developmental Increase in Ecto-5'-Nucleotidase Activity Overlaps with
 Appearance of Two Immunologically Distinct Enzyme Isoforms in Rat
 Hippocampal Synaptic Plasma Membranes" in Journal of Molecular Neuroscience, 54, no. 1 (2014):109-118,
https://doi.org/10.1007/s12031-014-0256-0 . .

TY  - JOUR
AU  - Savić, Danijela
AU  - Lavrnja, Irena
AU  - Dacic, Sanja
AU  - Bjelobaba, Ivana
AU  - Nedeljkovic, Nadezda
AU  - Stojiljkovic, Mirjana
AU  - Herdegen, Thomas
AU  - Peković, Sanja
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2263
AB  - Tiazofurin is a purine nucleoside analogue, with a broad spectrum of
   antitumoral and anti-inflammatory properties. In the present study, we
   have investigated the effect of tiazofurin on microglial inflammatory
   response to lipopolysaccharide in vitro. The cytotoxic effect of the
   drug was examined by sulforhodamine B assay. The Griess method was used
   to quantify nitrite production. Microglial morphology was assessed by
   measuring cell body size. Release of the pro-inflammatory cytokines,
   tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and the
   anti-inflammatory cytokine interleukin-10, were evaluated by
   enzyme-linked immunosorbent assay. Our data showed that tiazofurin
   decreased the number of activated microglia, lowered nitric oxide
   production and reduced the average cell surface of these cells.
   Tiazofurin reduced tumor necrosis factor-alpha, interleukin-6 and
   increased interleukin-10 secretion. Conversely, this drug promoted the
   release of interleukin-1 beta. Results obtained in this study indicate
   that TR displayed both anti-and pro-inflammatory modulation of activated
   microglia that could be relevant for its antitumor action within the
   central nervous system.
T2  - Archives of Biological Sciences
T1  - Tiazofurin modulates lipopolysaccharide-activated microglia in vitro
IS  - 4
VL  - 66
DO  - 10.2298/ABS1404633S
SP  - 1633
EP  - 1640
ER  - 

@article{
author = "Savić, Danijela and Lavrnja, Irena and Dacic, Sanja and Bjelobaba, Ivana and Nedeljkovic, Nadezda and Stojiljkovic, Mirjana and Herdegen, Thomas and Peković, Sanja",
year = "2014",
abstract = "Tiazofurin is a purine nucleoside analogue, with a broad spectrum of
   antitumoral and anti-inflammatory properties. In the present study, we
   have investigated the effect of tiazofurin on microglial inflammatory
   response to lipopolysaccharide in vitro. The cytotoxic effect of the
   drug was examined by sulforhodamine B assay. The Griess method was used
   to quantify nitrite production. Microglial morphology was assessed by
   measuring cell body size. Release of the pro-inflammatory cytokines,
   tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and the
   anti-inflammatory cytokine interleukin-10, were evaluated by
   enzyme-linked immunosorbent assay. Our data showed that tiazofurin
   decreased the number of activated microglia, lowered nitric oxide
   production and reduced the average cell surface of these cells.
   Tiazofurin reduced tumor necrosis factor-alpha, interleukin-6 and
   increased interleukin-10 secretion. Conversely, this drug promoted the
   release of interleukin-1 beta. Results obtained in this study indicate
   that TR displayed both anti-and pro-inflammatory modulation of activated
   microglia that could be relevant for its antitumor action within the
   central nervous system.",
journal = "Archives of Biological Sciences",
title = "Tiazofurin modulates lipopolysaccharide-activated microglia in vitro",
number = "4",
volume = "66",
doi = "10.2298/ABS1404633S",
pages = "1633-1640"
}

Savić, D., Lavrnja, I., Dacic, S., Bjelobaba, I., Nedeljkovic, N., Stojiljkovic, M., Herdegen, T.,& Peković, S.. (2014). Tiazofurin modulates lipopolysaccharide-activated microglia in vitro. in Archives of Biological Sciences, 66(4), 1633-1640.
https://doi.org/10.2298/ABS1404633S

Savić D, Lavrnja I, Dacic S, Bjelobaba I, Nedeljkovic N, Stojiljkovic M, Herdegen T, Peković S. Tiazofurin modulates lipopolysaccharide-activated microglia in vitro. in Archives of Biological Sciences. 2014;66(4):1633-1640.
doi:10.2298/ABS1404633S .

Savić, Danijela, Lavrnja, Irena, Dacic, Sanja, Bjelobaba, Ivana, Nedeljkovic, Nadezda, Stojiljkovic, Mirjana, Herdegen, Thomas, Peković, Sanja, "Tiazofurin modulates lipopolysaccharide-activated microglia in vitro" in Archives of Biological Sciences, 66, no. 4 (2014):1633-1640,
https://doi.org/10.2298/ABS1404633S . .

TY  - JOUR
AU  - Savić, Danijela
AU  - Stojiljkovic, Mirjana
AU  - Lavrnja, Irena
AU  - Parabucki, Ana
AU  - Bjelobaba, Ivana
AU  - Nedeljkovic, Nadezda
AU  - Herdegen, Thomas
AU  - Peković, Sanja
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2120
AB  - Ribavirin (RBV) is synthetic purine nucleoside analogue, licensed as
   anti-viral drug that displays immunomodulatory actions on various immune
   cells. Our previous ex vivo studies have demonstrated immunosuppressive
   effects of RBV on reactive T-lymphocytes in experimental autoimmune
   encephalomyelitis. Here, we examined the effects of RBV on inflammatory
   response of microglia. RBV potency to down-regulate microglia
   inflammatory response was assessed by measuring microglia cell body
   size, and the production of nitric oxide (NO) and pro-and
   anti-inflammatory cytokines. RBV exerted cytotoxic effects on
   LPS-stimulated microglia, leaving non-stimulated microglia unaffected.
   The exposure of activated microglia to RBV led to: decrease in the level
   of NO as a result of decreased cell number, lower average cell surface,
   the reduction of membrane ruffling, the suppression of interleukin-6
   release and promoted interleukin-10 production. On the other hand, RBV
   promoted LPS-induced interleukin-1 beta release. Our results imply that
   RBV is a complex immunomodulator showing both anti-and pro-inflammatory
   effects on activated microglia.
T2  - Immunopharmacology and Immunotoxicology
T1  - Ribavirin shows immunomodulatory effects on activated microglia
IS  - 6
VL  - 36
DO  - 10.3109/08923973.2014.971962
SP  - 433
EP  - 441
ER  - 

@article{
author = "Savić, Danijela and Stojiljkovic, Mirjana and Lavrnja, Irena and Parabucki, Ana and Bjelobaba, Ivana and Nedeljkovic, Nadezda and Herdegen, Thomas and Peković, Sanja",
year = "2014",
abstract = "Ribavirin (RBV) is synthetic purine nucleoside analogue, licensed as
   anti-viral drug that displays immunomodulatory actions on various immune
   cells. Our previous ex vivo studies have demonstrated immunosuppressive
   effects of RBV on reactive T-lymphocytes in experimental autoimmune
   encephalomyelitis. Here, we examined the effects of RBV on inflammatory
   response of microglia. RBV potency to down-regulate microglia
   inflammatory response was assessed by measuring microglia cell body
   size, and the production of nitric oxide (NO) and pro-and
   anti-inflammatory cytokines. RBV exerted cytotoxic effects on
   LPS-stimulated microglia, leaving non-stimulated microglia unaffected.
   The exposure of activated microglia to RBV led to: decrease in the level
   of NO as a result of decreased cell number, lower average cell surface,
   the reduction of membrane ruffling, the suppression of interleukin-6
   release and promoted interleukin-10 production. On the other hand, RBV
   promoted LPS-induced interleukin-1 beta release. Our results imply that
   RBV is a complex immunomodulator showing both anti-and pro-inflammatory
   effects on activated microglia.",
journal = "Immunopharmacology and Immunotoxicology",
title = "Ribavirin shows immunomodulatory effects on activated microglia",
number = "6",
volume = "36",
doi = "10.3109/08923973.2014.971962",
pages = "433-441"
}

Savić, D., Stojiljkovic, M., Lavrnja, I., Parabucki, A., Bjelobaba, I., Nedeljkovic, N., Herdegen, T.,& Peković, S.. (2014). Ribavirin shows immunomodulatory effects on activated microglia. in Immunopharmacology and Immunotoxicology, 36(6), 433-441.
https://doi.org/10.3109/08923973.2014.971962

Savić D, Stojiljkovic M, Lavrnja I, Parabucki A, Bjelobaba I, Nedeljkovic N, Herdegen T, Peković S. Ribavirin shows immunomodulatory effects on activated microglia. in Immunopharmacology and Immunotoxicology. 2014;36(6):433-441.
doi:10.3109/08923973.2014.971962 .

Savić, Danijela, Stojiljkovic, Mirjana, Lavrnja, Irena, Parabucki, Ana, Bjelobaba, Ivana, Nedeljkovic, Nadezda, Herdegen, Thomas, Peković, Sanja, "Ribavirin shows immunomodulatory effects on activated microglia" in Immunopharmacology and Immunotoxicology, 36, no. 6 (2014):433-441,
https://doi.org/10.3109/08923973.2014.971962 . .