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  - CONF
AU  - Laketa, Danijela
AU  - Manojlović-Stojanoski, Milica
AU  - Lavrnja, Irena
AU  - Stevanović, Ivana
AU  - Trifunović, Svetlana
AU  - Ristić, Nataša
AU  - Nestorović, Nataša
AU  - Sévigny, Jean
AU  - Nedeljković, Nadežda
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6209
AB  - To accelerate organ maturation and prevent complications due to preterm birth, antenatal treatment with
synthetic glucocorticoids (GCs – dexamethasone or betamethasone) is usually given between the 24th
and 34th week of pregnancy to women at risk of delivery within the next seven days [1]. Despite recommendations,
repeat courses of antenatal GCs are frequently given, although excessive GC stimulation may
exert adverse neurodevelopmental effects [1]. The purinergic system is essential for neurodevelopment
[2]. Extracellular purine levels are regulated by ectonucleotidases, with ectonucleoside triphosphate diphosphohydrolase
1 (NTPDase1/CD39) and ecto-5ʹ-nucleotidase (e5ʹNT/CD73), abundant in the CNS,
which jointly hydrolyze ATP to adenosine. Both ectonucleotidases are also involved in cell adhesion
and migration [3]. We aimed to explore the effects of antenatal dexamethasone (DEX) treatment on the
expression and enzymatic activity of NTPDase1/e5ʹNT tandem in the rat fetal brain. Wistar rat dams were
treated with 0.5 mg/kg DEX, at gestation day (GD) 16, 17, and 18. We found sex-specific male-biased
upregulation of CD39 and CD73 mRNA and protein abundances, and an increase in the corresponding enzymatic activities in the rat fetal brain at GD21, induced by antenatal DEX treatment. Observed changes
indicate a possible decrease in P2, and an increase in P1 purinergic receptors-mediated signaling, as
well as a potential decrease in migration of progenitor cells, particularly pronounced in the brain of male
fetuses. Together, sex-dependent induction of CD39 and CD73 might interfere with neurodevelopmental
processes, thus contributing to adverse effects of antenatal DEX treatment, especially in males.
PB  - Federation of European Neuroscience Societies
C3  - Book of Abstracts: Virtual FENS Regional Meeting 2021; 2021 Aug 25-27; Krakow, Poland
T1  - NTPDase1/CD39 and Ecto-5ʹ-nucleotidase/CD73 are Upregulated in a Sex-specific fashion in the Rat Fetal Brain After Repeated Antenatal Dexamethasone Treatment
SP  - 192
EP  - 193
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6209
ER  - 

@conference{
author = "Laketa, Danijela and Manojlović-Stojanoski, Milica and Lavrnja, Irena and Stevanović, Ivana and Trifunović, Svetlana and Ristić, Nataša and Nestorović, Nataša and Sévigny, Jean and Nedeljković, Nadežda",
year = "2021",
abstract = "To accelerate organ maturation and prevent complications due to preterm birth, antenatal treatment with
synthetic glucocorticoids (GCs – dexamethasone or betamethasone) is usually given between the 24th
and 34th week of pregnancy to women at risk of delivery within the next seven days [1]. Despite recommendations,
repeat courses of antenatal GCs are frequently given, although excessive GC stimulation may
exert adverse neurodevelopmental effects [1]. The purinergic system is essential for neurodevelopment
[2]. Extracellular purine levels are regulated by ectonucleotidases, with ectonucleoside triphosphate diphosphohydrolase
1 (NTPDase1/CD39) and ecto-5ʹ-nucleotidase (e5ʹNT/CD73), abundant in the CNS,
which jointly hydrolyze ATP to adenosine. Both ectonucleotidases are also involved in cell adhesion
and migration [3]. We aimed to explore the effects of antenatal dexamethasone (DEX) treatment on the
expression and enzymatic activity of NTPDase1/e5ʹNT tandem in the rat fetal brain. Wistar rat dams were
treated with 0.5 mg/kg DEX, at gestation day (GD) 16, 17, and 18. We found sex-specific male-biased
upregulation of CD39 and CD73 mRNA and protein abundances, and an increase in the corresponding enzymatic activities in the rat fetal brain at GD21, induced by antenatal DEX treatment. Observed changes
indicate a possible decrease in P2, and an increase in P1 purinergic receptors-mediated signaling, as
well as a potential decrease in migration of progenitor cells, particularly pronounced in the brain of male
fetuses. Together, sex-dependent induction of CD39 and CD73 might interfere with neurodevelopmental
processes, thus contributing to adverse effects of antenatal DEX treatment, especially in males.",
publisher = "Federation of European Neuroscience Societies",
journal = "Book of Abstracts: Virtual FENS Regional Meeting 2021; 2021 Aug 25-27; Krakow, Poland",
title = "NTPDase1/CD39 and Ecto-5ʹ-nucleotidase/CD73 are Upregulated in a Sex-specific fashion in the Rat Fetal Brain After Repeated Antenatal Dexamethasone Treatment",
pages = "192-193",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6209"
}

Laketa, D., Manojlović-Stojanoski, M., Lavrnja, I., Stevanović, I., Trifunović, S., Ristić, N., Nestorović, N., Sévigny, J.,& Nedeljković, N.. (2021). NTPDase1/CD39 and Ecto-5ʹ-nucleotidase/CD73 are Upregulated in a Sex-specific fashion in the Rat Fetal Brain After Repeated Antenatal Dexamethasone Treatment. in Book of Abstracts: Virtual FENS Regional Meeting 2021; 2021 Aug 25-27; Krakow, Poland
Federation of European Neuroscience Societies., 192-193.
https://hdl.handle.net/21.15107/rcub_ibiss_6209

Laketa D, Manojlović-Stojanoski M, Lavrnja I, Stevanović I, Trifunović S, Ristić N, Nestorović N, Sévigny J, Nedeljković N. NTPDase1/CD39 and Ecto-5ʹ-nucleotidase/CD73 are Upregulated in a Sex-specific fashion in the Rat Fetal Brain After Repeated Antenatal Dexamethasone Treatment. in Book of Abstracts: Virtual FENS Regional Meeting 2021; 2021 Aug 25-27; Krakow, Poland. 2021;:192-193.
https://hdl.handle.net/21.15107/rcub_ibiss_6209 .

Laketa, Danijela, Manojlović-Stojanoski, Milica, Lavrnja, Irena, Stevanović, Ivana, Trifunović, Svetlana, Ristić, Nataša, Nestorović, Nataša, Sévigny, Jean, Nedeljković, Nadežda, "NTPDase1/CD39 and Ecto-5ʹ-nucleotidase/CD73 are Upregulated in a Sex-specific fashion in the Rat Fetal Brain After Repeated Antenatal Dexamethasone Treatment" in Book of Abstracts: Virtual FENS Regional Meeting 2021; 2021 Aug 25-27; Krakow, Poland (2021):192-193,
https://hdl.handle.net/21.15107/rcub_ibiss_6209 .

TY  - CONF
AU  - Božić, Iva
AU  - Milošević, Katarina
AU  - Janjić, Marija
AU  - Savić, Danijela
AU  - Laketa, Danijela
AU  - Jakovljević, Marija
AU  - Milošević, Ana
AU  - Peković, Sanja
AU  - Lavrnja, Irena
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6006
AB  - Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination, neurodegeneration and gliosis. It is considered as a perplexing multifactorial disease in which the neuroendocrine system plays an important role. Growth hormone (GH) is synthesized and secreted by the somatotroph cells of the anterior pituitary. GH secretion is positively regulated by the hypothalamic factor GHRH and exerts its effects through interaction with the GH receptor (GHR), a member of the class I cytokine receptor family. It was demonstrated that neurons and astrocytes also produce GH and that GHR is widely expressed in the CNS. Nonetheless, it is not known whether expression pattern of GHR changes in the CNS during MS. We investigated GHR expression in the spinal cord during the course of experimental autoimmune encephalomyelitis (EAE), animal model of MS that is broadly used. Our results show that GHR is diminished on mRNA and protein level during EAE. Double immunofluorescence studies demonstrated that GHR is expressed in different cell types in the spinal cord in physiological conditions, including astrocytes and microglia. This expression pattern does not change extensively after the onset of EAE. However, at the peak of disease GHR is absent from astrocytes in the white and grey matter, but still present in microglia, although to a lesser degree. At the end of disease, when the animals have recovered, GHR expression is similar to control conditions. Our results point to complex involvement of GHR in the pathology of EAE.
PB  - Belgrade : Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - Expression of growth hormone receptor (GHR) in experimental autoimmune encephalomyelitis
EP  - 212
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6006
ER  - 

@conference{
author = "Božić, Iva and Milošević, Katarina and Janjić, Marija and Savić, Danijela and Laketa, Danijela and Jakovljević, Marija and Milošević, Ana and Peković, Sanja and Lavrnja, Irena",
year = "2019",
abstract = "Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination, neurodegeneration and gliosis. It is considered as a perplexing multifactorial disease in which the neuroendocrine system plays an important role. Growth hormone (GH) is synthesized and secreted by the somatotroph cells of the anterior pituitary. GH secretion is positively regulated by the hypothalamic factor GHRH and exerts its effects through interaction with the GH receptor (GHR), a member of the class I cytokine receptor family. It was demonstrated that neurons and astrocytes also produce GH and that GHR is widely expressed in the CNS. Nonetheless, it is not known whether expression pattern of GHR changes in the CNS during MS. We investigated GHR expression in the spinal cord during the course of experimental autoimmune encephalomyelitis (EAE), animal model of MS that is broadly used. Our results show that GHR is diminished on mRNA and protein level during EAE. Double immunofluorescence studies demonstrated that GHR is expressed in different cell types in the spinal cord in physiological conditions, including astrocytes and microglia. This expression pattern does not change extensively after the onset of EAE. However, at the peak of disease GHR is absent from astrocytes in the white and grey matter, but still present in microglia, although to a lesser degree. At the end of disease, when the animals have recovered, GHR expression is similar to control conditions. Our results point to complex involvement of GHR in the pathology of EAE.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "Expression of growth hormone receptor (GHR) in experimental autoimmune encephalomyelitis",
pages = "212",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6006"
}

Božić, I., Milošević, K., Janjić, M., Savić, D., Laketa, D., Jakovljević, M., Milošević, A., Peković, S.,& Lavrnja, I.. (2019). Expression of growth hormone receptor (GHR) in experimental autoimmune encephalomyelitis. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade : Serbian Neuroscience Society..
https://hdl.handle.net/21.15107/rcub_ibiss_6006

Božić I, Milošević K, Janjić M, Savić D, Laketa D, Jakovljević M, Milošević A, Peković S, Lavrnja I. Expression of growth hormone receptor (GHR) in experimental autoimmune encephalomyelitis. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:null-212.
https://hdl.handle.net/21.15107/rcub_ibiss_6006 .

Božić, Iva, Milošević, Katarina, Janjić, Marija, Savić, Danijela, Laketa, Danijela, Jakovljević, Marija, Milošević, Ana, Peković, Sanja, Lavrnja, Irena, "Expression of growth hormone receptor (GHR) in experimental autoimmune encephalomyelitis" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019),
https://hdl.handle.net/21.15107/rcub_ibiss_6006 .

TY  - CONF
AU  - Milošević, Katarina
AU  - Lavrnja, Irena
AU  - Janjić, Marija
AU  - Božić, Iva
AU  - Laketa, Danijela
AU  - Dacić, Sanja
AU  - Peković, Sanja
AU  - Savić, Danijela
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6004
AB  - Traumatic brain injury triggers neuroinflammatory response mediated by distinct populations of myeloid cells, including central nervous system (CNS) resident macrophages - microglia. Depending on the time upon insult this response may either contribute to restorative effects or hinder CNS repair.
Therefore, the focus of this study was on determining temporal course in gene expression profiles of markers specific to the mononuclear phagocyte system (MPS).
We have used the model of cortical stab injury which was performed on 3-months-old male Wistar rats. All animals were divided into 3 experimental groups: control, sham and lesion group and sacrificed at 1, 2, 3 and 7 days post-injury. After brain isolation, mRNA was extracted from cortical pieces around the center of lesion (the same tissue part was used for sham and control groups). The gene expression was analyzed by real-time PCR.
The mRNA levels of Itgam, Aif-1, Cd68 and Cx3Cr1, which are surface markers of MPS, were increased in first two days after brain injury, and then all, except Cd68, showed declining trend compared to control group. Furthermore, we analyzed expression of Arg-1, Il-6 and Tnf-alpha genes, which could be indicators of pro- or anti-inflammatory milieu. All of them increased significantly in the first two days post-injury, and then returned to control level, with the most prominent changes detected in Arg-1 mRNA level.
This study indicates enhanced MPS response in the acute phase after cortical stab injury. Further studies are required to determine which populations of CNS myeloid cells predominate in specific time point upon injury.
PB  - Belgrade : Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - Mononuclear Phagocyte System In Traumatic Brain Injury
SP  - 503
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6004
ER  - 

@conference{
author = "Milošević, Katarina and Lavrnja, Irena and Janjić, Marija and Božić, Iva and Laketa, Danijela and Dacić, Sanja and Peković, Sanja and Savić, Danijela",
year = "2019",
abstract = "Traumatic brain injury triggers neuroinflammatory response mediated by distinct populations of myeloid cells, including central nervous system (CNS) resident macrophages - microglia. Depending on the time upon insult this response may either contribute to restorative effects or hinder CNS repair.
Therefore, the focus of this study was on determining temporal course in gene expression profiles of markers specific to the mononuclear phagocyte system (MPS).
We have used the model of cortical stab injury which was performed on 3-months-old male Wistar rats. All animals were divided into 3 experimental groups: control, sham and lesion group and sacrificed at 1, 2, 3 and 7 days post-injury. After brain isolation, mRNA was extracted from cortical pieces around the center of lesion (the same tissue part was used for sham and control groups). The gene expression was analyzed by real-time PCR.
The mRNA levels of Itgam, Aif-1, Cd68 and Cx3Cr1, which are surface markers of MPS, were increased in first two days after brain injury, and then all, except Cd68, showed declining trend compared to control group. Furthermore, we analyzed expression of Arg-1, Il-6 and Tnf-alpha genes, which could be indicators of pro- or anti-inflammatory milieu. All of them increased significantly in the first two days post-injury, and then returned to control level, with the most prominent changes detected in Arg-1 mRNA level.
This study indicates enhanced MPS response in the acute phase after cortical stab injury. Further studies are required to determine which populations of CNS myeloid cells predominate in specific time point upon injury.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "Mononuclear Phagocyte System In Traumatic Brain Injury",
pages = "503",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6004"
}

Milošević, K., Lavrnja, I., Janjić, M., Božić, I., Laketa, D., Dacić, S., Peković, S.,& Savić, D.. (2019). Mononuclear Phagocyte System In Traumatic Brain Injury. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade : Serbian Neuroscience Society., 503.
https://hdl.handle.net/21.15107/rcub_ibiss_6004

Milošević K, Lavrnja I, Janjić M, Božić I, Laketa D, Dacić S, Peković S, Savić D. Mononuclear Phagocyte System In Traumatic Brain Injury. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:503.
https://hdl.handle.net/21.15107/rcub_ibiss_6004 .

Milošević, Katarina, Lavrnja, Irena, Janjić, Marija, Božić, Iva, Laketa, Danijela, Dacić, Sanja, Peković, Sanja, Savić, Danijela, "Mononuclear Phagocyte System In Traumatic Brain Injury" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):503,
https://hdl.handle.net/21.15107/rcub_ibiss_6004 .