TY  - CONF
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Lavrnja, Irena
AU  - Savić, Danijela
AU  - Milošević, Katarina
AU  - Bjelobaba, Ivana
PY  - 2024
UR  - https://www.neurosteroids.unito.it/home-page
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6583
AB  - Experimental autoimmune encephalomyelitis (EAE) is the most commonly used animal
model of multiple sclerosis (MS) [1], which is a chronic neurodegenerative disease of the
central nervous system characterized with neuroinflammation and demyelination. MS
affects over 2 million people worldwide, mostly during the reproductive age, and it is far
more prevalent in women than in men [3]. Because fluctuations in sex hormone levels
during puberty, menarche, pregnancy, or menopause may impact the prevalence and
outcome of MS [2], we have undertaken efforts to elucidate the status of female
hypothalamic-pituitary-gonadal (HPG) axis during EAE.
EAE was induced by active immunization in 9-12-week-old female rats of Dark Agouti
strain. Disease symptoms, body weight changes and estrous cycle stages were monitored
daily. The animals were sacrificed at the onset of symptoms (Onset), at the peak of the
disease (Peak) and after the complete cessation of all symptoms (End). Non-immunized,
age-matched female rats were used as the Control group. All animals were sacrificed in the
diestrus stage of the estrous cycle. Luteinizing hormone (LH) and gonadal steroid levels
were measured, and the expression of relevant genes was assessed in hypothalamic, pituitary
and ovarian tissue.
In the hypothalamic tissue, a downregulation in Kiss1 expression was observed, while
Gnrh1 expression remained unaffected during the symptomatic phase of EAE. This was
accompanied by several-fold induction of the expression of astrocytes and
microglia/macrophages inflammatory markers – Gfap, Cd68, Ccl2, and Il1b. In the anterior
pituitary tissue, a downregulation in the expression of Gnrhr, Lhb and Cga was recorded,
along with significantly decreased LH levels in the circulation, at the peak of EAE.
Nevertheless, pituitary remained responsive to GnRH analogue challenge during the peak of
the disease. Pituitary Fshb was upregulated during onset and peak of EAE. An arrest in the
estrous cycle was registered, at the state of diestrus. Histological analysis of ovaries showed
maintenance of corpora lutea and increased number of atretic follicles at the peak of the
disease. In the ovarian tissue, steroidogenic machinery components – StAR, CYP11A1 and
3β-HSD, were upregulated at the gene and/or protein level. Accordingly, progesterone
levels were increased during the symptomatic phase of EAE, both in circulation and in
ovarian tissue. CYP17A1 gene and protein as well as testosterone and estradiol levels in the
ovary were significantly decreased. Interestingly, circulating testosterone levels were
slightly increased while circulating estradiol remained unchanged during EAE.
Overall, our results suggest that the changes in the function of the female reproductive axis
during EAE are due to a disruption of hypothalamic regulation, probably caused by
neuroinflammation. The arrest in the diestrus phase of the estrous cycle, together with
changes in ovarian steroidogenesis, contributes to a pseudopregnancy-like state in female
rats, which could represent an adaptation to the inflammatory process and implies a
temporary reduction in reproductive capacity to allow the system to fight the disease.
Furthermore, our results point to the importance of investigating the bidirectional
relationship between hormonal status and EAE/MS. This may also have an impact in the
clinical practice, as the approval of sex steroids as adjuvant therapy for MS could be
accelerated if they were prescribed only after careful monitoring of the individual patient’s
HPG axis status.
PB  - Milan: Dipartimento di Scienze Farmacologiche e Biomolecolari
C3  - Abstract of individual lectures and free contributions: 12th International Meeting Steroids and Nervous System; 2024 Feb 24-27; Torino, Italy
T1  - Hypothalamic-Pituitary-Ovarian Axis Is Affected in Dark Agouti Rats With Experimental Autoimmune Encephalomyelitis
SP  - 127
EP  - 128
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6583
ER  - 

@conference{
author = "Milošević, Ana and Janjić, Marija and Lavrnja, Irena and Savić, Danijela and Milošević, Katarina and Bjelobaba, Ivana",
year = "2024",
abstract = "Experimental autoimmune encephalomyelitis (EAE) is the most commonly used animal
model of multiple sclerosis (MS) [1], which is a chronic neurodegenerative disease of the
central nervous system characterized with neuroinflammation and demyelination. MS
affects over 2 million people worldwide, mostly during the reproductive age, and it is far
more prevalent in women than in men [3]. Because fluctuations in sex hormone levels
during puberty, menarche, pregnancy, or menopause may impact the prevalence and
outcome of MS [2], we have undertaken efforts to elucidate the status of female
hypothalamic-pituitary-gonadal (HPG) axis during EAE.
EAE was induced by active immunization in 9-12-week-old female rats of Dark Agouti
strain. Disease symptoms, body weight changes and estrous cycle stages were monitored
daily. The animals were sacrificed at the onset of symptoms (Onset), at the peak of the
disease (Peak) and after the complete cessation of all symptoms (End). Non-immunized,
age-matched female rats were used as the Control group. All animals were sacrificed in the
diestrus stage of the estrous cycle. Luteinizing hormone (LH) and gonadal steroid levels
were measured, and the expression of relevant genes was assessed in hypothalamic, pituitary
and ovarian tissue.
In the hypothalamic tissue, a downregulation in Kiss1 expression was observed, while
Gnrh1 expression remained unaffected during the symptomatic phase of EAE. This was
accompanied by several-fold induction of the expression of astrocytes and
microglia/macrophages inflammatory markers – Gfap, Cd68, Ccl2, and Il1b. In the anterior
pituitary tissue, a downregulation in the expression of Gnrhr, Lhb and Cga was recorded,
along with significantly decreased LH levels in the circulation, at the peak of EAE.
Nevertheless, pituitary remained responsive to GnRH analogue challenge during the peak of
the disease. Pituitary Fshb was upregulated during onset and peak of EAE. An arrest in the
estrous cycle was registered, at the state of diestrus. Histological analysis of ovaries showed
maintenance of corpora lutea and increased number of atretic follicles at the peak of the
disease. In the ovarian tissue, steroidogenic machinery components – StAR, CYP11A1 and
3β-HSD, were upregulated at the gene and/or protein level. Accordingly, progesterone
levels were increased during the symptomatic phase of EAE, both in circulation and in
ovarian tissue. CYP17A1 gene and protein as well as testosterone and estradiol levels in the
ovary were significantly decreased. Interestingly, circulating testosterone levels were
slightly increased while circulating estradiol remained unchanged during EAE.
Overall, our results suggest that the changes in the function of the female reproductive axis
during EAE are due to a disruption of hypothalamic regulation, probably caused by
neuroinflammation. The arrest in the diestrus phase of the estrous cycle, together with
changes in ovarian steroidogenesis, contributes to a pseudopregnancy-like state in female
rats, which could represent an adaptation to the inflammatory process and implies a
temporary reduction in reproductive capacity to allow the system to fight the disease.
Furthermore, our results point to the importance of investigating the bidirectional
relationship between hormonal status and EAE/MS. This may also have an impact in the
clinical practice, as the approval of sex steroids as adjuvant therapy for MS could be
accelerated if they were prescribed only after careful monitoring of the individual patient’s
HPG axis status.",
publisher = "Milan: Dipartimento di Scienze Farmacologiche e Biomolecolari",
journal = "Abstract of individual lectures and free contributions: 12th International Meeting Steroids and Nervous System; 2024 Feb 24-27; Torino, Italy",
title = "Hypothalamic-Pituitary-Ovarian Axis Is Affected in Dark Agouti Rats With Experimental Autoimmune Encephalomyelitis",
pages = "127-128",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6583"
}

Milošević, A., Janjić, M., Lavrnja, I., Savić, D., Milošević, K.,& Bjelobaba, I.. (2024). Hypothalamic-Pituitary-Ovarian Axis Is Affected in Dark Agouti Rats With Experimental Autoimmune Encephalomyelitis. in Abstract of individual lectures and free contributions: 12th International Meeting Steroids and Nervous System; 2024 Feb 24-27; Torino, Italy
Milan: Dipartimento di Scienze Farmacologiche e Biomolecolari., 127-128.
https://hdl.handle.net/21.15107/rcub_ibiss_6583

Milošević A, Janjić M, Lavrnja I, Savić D, Milošević K, Bjelobaba I. Hypothalamic-Pituitary-Ovarian Axis Is Affected in Dark Agouti Rats With Experimental Autoimmune Encephalomyelitis. in Abstract of individual lectures and free contributions: 12th International Meeting Steroids and Nervous System; 2024 Feb 24-27; Torino, Italy. 2024;:127-128.
https://hdl.handle.net/21.15107/rcub_ibiss_6583 .

Milošević, Ana, Janjić, Marija, Lavrnja, Irena, Savić, Danijela, Milošević, Katarina, Bjelobaba, Ivana, "Hypothalamic-Pituitary-Ovarian Axis Is Affected in Dark Agouti Rats With Experimental Autoimmune Encephalomyelitis" in Abstract of individual lectures and free contributions: 12th International Meeting Steroids and Nervous System; 2024 Feb 24-27; Torino, Italy (2024):127-128,
https://hdl.handle.net/21.15107/rcub_ibiss_6583 .

TY  - CONF
AU  - Milošević, Ana
AU  - Savić, Danijela
AU  - Lavrnja, Irena
AU  - Milošević, Katarina
AU  - Bjelobaba, Ivana
AU  - Janjić, Marija
PY  - 2024
UR  - https://www.neurosteroids.unito.it/home-page
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6582
AB  - Multiple sclerosis (MS) is an autoimmune disease that usually occurs in both sexes during
the reproductive years. Various neuroendocrine changes have been described in this
inflammatory, demyelinating and debilitating disease, and many male MS patients have
lower blood testosterone levels. Our aim was to determine the extent of alterations in the
hypothalamic-pituitary-gonadal axis in the male rat model of MS, experimental autoimmune
encephalomyelitis (EAE). During the course of the disease, hypothalamic tissue showed a
transient upregulation of the inflammatory marker genes Gfap, Cd68, Ccl2 and Il1b,
accompanied by a downregulation of Gnrh1 expression and pituitary Gnrhr expression.
Serum levels of luteinizing hormone and testosterone were also reduced during the disease.
To better understand the causes of decreased testosterone production during EAE, we
examined the expression status of genes and proteins associated with steroidogenesis in the
testes. No changes in the number of interstitial cells were detected in the EAE animals, but
the expression of the gene insulin-like 3 was reduced at the peak of the disease, suggesting
that the functional capacity of Leydig cells was impaired. Consistent with this finding, the
expression of most steroidogenic enzyme genes and proteins was reduced during EAE,
including StAR, CYP11A1, CYP17A1 and HSD3B. No signs of testicular inflammation
were observed. Steroidogenesis recovered after the injection of hCG, a placental
gonadotropin or buserelin acetate, an analogue of gonadotropin-releasing hormone, at the
peak of EAE. Overall, our results are consistent with the hypothesis that impaired testicular
steroidogenesis originates upstream of the testes and that low serum LH levels are the main
cause of decreased testosterone levels during EAE.
PB  - Milan: Dipartimento di Scienze Farmacologiche e Biomolecolari
C3  - Abstract of individual lectures and free contributions: 12th International Meeting Steroids and Nervous System; 2024 Feb 24-27; Torino, Italy
T1  - The Hypothalamic-Pituitary-Gonadal Axis Is Suppressed During Experimental Autoimmune Encephalomyelitis in Male Rats
SP  - 124
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6582
ER  - 

@conference{
author = "Milošević, Ana and Savić, Danijela and Lavrnja, Irena and Milošević, Katarina and Bjelobaba, Ivana and Janjić, Marija",
year = "2024",
abstract = "Multiple sclerosis (MS) is an autoimmune disease that usually occurs in both sexes during
the reproductive years. Various neuroendocrine changes have been described in this
inflammatory, demyelinating and debilitating disease, and many male MS patients have
lower blood testosterone levels. Our aim was to determine the extent of alterations in the
hypothalamic-pituitary-gonadal axis in the male rat model of MS, experimental autoimmune
encephalomyelitis (EAE). During the course of the disease, hypothalamic tissue showed a
transient upregulation of the inflammatory marker genes Gfap, Cd68, Ccl2 and Il1b,
accompanied by a downregulation of Gnrh1 expression and pituitary Gnrhr expression.
Serum levels of luteinizing hormone and testosterone were also reduced during the disease.
To better understand the causes of decreased testosterone production during EAE, we
examined the expression status of genes and proteins associated with steroidogenesis in the
testes. No changes in the number of interstitial cells were detected in the EAE animals, but
the expression of the gene insulin-like 3 was reduced at the peak of the disease, suggesting
that the functional capacity of Leydig cells was impaired. Consistent with this finding, the
expression of most steroidogenic enzyme genes and proteins was reduced during EAE,
including StAR, CYP11A1, CYP17A1 and HSD3B. No signs of testicular inflammation
were observed. Steroidogenesis recovered after the injection of hCG, a placental
gonadotropin or buserelin acetate, an analogue of gonadotropin-releasing hormone, at the
peak of EAE. Overall, our results are consistent with the hypothesis that impaired testicular
steroidogenesis originates upstream of the testes and that low serum LH levels are the main
cause of decreased testosterone levels during EAE.",
publisher = "Milan: Dipartimento di Scienze Farmacologiche e Biomolecolari",
journal = "Abstract of individual lectures and free contributions: 12th International Meeting Steroids and Nervous System; 2024 Feb 24-27; Torino, Italy",
title = "The Hypothalamic-Pituitary-Gonadal Axis Is Suppressed During Experimental Autoimmune Encephalomyelitis in Male Rats",
pages = "124",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6582"
}

Milošević, A., Savić, D., Lavrnja, I., Milošević, K., Bjelobaba, I.,& Janjić, M.. (2024). The Hypothalamic-Pituitary-Gonadal Axis Is Suppressed During Experimental Autoimmune Encephalomyelitis in Male Rats. in Abstract of individual lectures and free contributions: 12th International Meeting Steroids and Nervous System; 2024 Feb 24-27; Torino, Italy
Milan: Dipartimento di Scienze Farmacologiche e Biomolecolari., 124.
https://hdl.handle.net/21.15107/rcub_ibiss_6582

Milošević A, Savić D, Lavrnja I, Milošević K, Bjelobaba I, Janjić M. The Hypothalamic-Pituitary-Gonadal Axis Is Suppressed During Experimental Autoimmune Encephalomyelitis in Male Rats. in Abstract of individual lectures and free contributions: 12th International Meeting Steroids and Nervous System; 2024 Feb 24-27; Torino, Italy. 2024;:124.
https://hdl.handle.net/21.15107/rcub_ibiss_6582 .

Milošević, Ana, Savić, Danijela, Lavrnja, Irena, Milošević, Katarina, Bjelobaba, Ivana, Janjić, Marija, "The Hypothalamic-Pituitary-Gonadal Axis Is Suppressed During Experimental Autoimmune Encephalomyelitis in Male Rats" in Abstract of individual lectures and free contributions: 12th International Meeting Steroids and Nervous System; 2024 Feb 24-27; Torino, Italy (2024):124,
https://hdl.handle.net/21.15107/rcub_ibiss_6582 .

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  - Božić, Iva
AU  - Lavrnja, Irena
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6369
AB  - Thiamine, also known as vitamin B1, is an essential nutrient that plays a crucial role in energy
metabolism and overall health. It is a water-soluble vitamin that plays an important role in the
conversion of carbohydrates into energy in the body. Thiamine is essential for the proper functioning of the nervous system, heart and muscles. Thiamine deficiency is a life-threatening disease
that leads to various disorders and lesions in the nerves and brain, at least in vertebrates. Several
thiamine precursors with higher bioavailability have been developed to compensate for thiamine
deficiency, including benfotiamine. Benfotiamine is more bioavailable and has higher tissue
penetration than thiamine. Studies have shown its antioxidant and anti-inflammatory potential in
activated immune and glial cells. It also improves complications observed in type 2 diabetes and
has beneficial effects in mouse models of neurodegenerative disease. Benfotiamine represents an
off-the-shelf agent used to support nerve health, promote healthy aging and support glucose
metabolism. Accordingly, the present review aimed to provide an overview of the neuroprotective
effects of thiamine/benfotiamine in the context of inflammation and oxidative stress.
PB  - Elsevier
T2  - Heliyon
T1  - Thiamine and benfotiamine: Focus on their therapeutic potential
IS  - 11
VL  - 9
DO  - 10.1016/j.heliyon.2023.e21839
SP  - e21839
ER  - 

@article{
author = "Božić, Iva and Lavrnja, Irena",
year = "2023",
abstract = "Thiamine, also known as vitamin B1, is an essential nutrient that plays a crucial role in energy
metabolism and overall health. It is a water-soluble vitamin that plays an important role in the
conversion of carbohydrates into energy in the body. Thiamine is essential for the proper functioning of the nervous system, heart and muscles. Thiamine deficiency is a life-threatening disease
that leads to various disorders and lesions in the nerves and brain, at least in vertebrates. Several
thiamine precursors with higher bioavailability have been developed to compensate for thiamine
deficiency, including benfotiamine. Benfotiamine is more bioavailable and has higher tissue
penetration than thiamine. Studies have shown its antioxidant and anti-inflammatory potential in
activated immune and glial cells. It also improves complications observed in type 2 diabetes and
has beneficial effects in mouse models of neurodegenerative disease. Benfotiamine represents an
off-the-shelf agent used to support nerve health, promote healthy aging and support glucose
metabolism. Accordingly, the present review aimed to provide an overview of the neuroprotective
effects of thiamine/benfotiamine in the context of inflammation and oxidative stress.",
publisher = "Elsevier",
journal = "Heliyon",
title = "Thiamine and benfotiamine: Focus on their therapeutic potential",
number = "11",
volume = "9",
doi = "10.1016/j.heliyon.2023.e21839",
pages = "e21839"
}

Božić, I.,& Lavrnja, I.. (2023). Thiamine and benfotiamine: Focus on their therapeutic potential. in Heliyon
Elsevier., 9(11), e21839.
https://doi.org/10.1016/j.heliyon.2023.e21839

Božić I, Lavrnja I. Thiamine and benfotiamine: Focus on their therapeutic potential. in Heliyon. 2023;9(11):e21839.
doi:10.1016/j.heliyon.2023.e21839 .

Božić, Iva, Lavrnja, Irena, "Thiamine and benfotiamine: Focus on their therapeutic potential" in Heliyon, 9, no. 11 (2023):e21839,
https://doi.org/10.1016/j.heliyon.2023.e21839 . .

TY  - CONF
AU  - Milošević, Katarina
AU  - Milošević, Ana
AU  - Živković, Anica
AU  - Stevanović, Ivana
AU  - Laketa, Danijela
AU  - Božić, Iva
AU  - Janjić, Marija
AU  - Bjelobaba, Ivana
AU  - Lavrnja, Irena
AU  - Savić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5875
AB  - Oxidative burst is a component of neuroinflammation whereby microglia-generated reactive oxygen species (ROS) either target pathogens or act as secondary messengers for microglial activation. In response to increased ROS during microglial activation, cytoprotective mechanisms are initiated primarily via Nrf2 activation and HO-1 expression. Agmatine is known to exert neuroprotective effect in vivo due to Nrf2 induction. While agmatine has been shown to activate the Nrf2/HO-1 signaling and protect macrophages from Lps-induced inflammation in vitro, its interaction with this pathway in activated microglia remains unexplored. Therefore, we sought to examine the potential of 100 μM agmatine as a pretreatment of Lps to activate Nrf2 in BV-2 microglia. In addition to cell viability, we analyzed the nuclear level of Nrf2 by Western blot and the expression of Hmox1 by PCR, as well as the protein level of HO-1. We also measured indicators of prooxidant and antioxidant activity: 4-HNE and total glutathione, respectively. Agmatine induces oxidative stress in non-stimulated microglia, as confirmed by the increase in the lipid peroxidation marker — 4-HNE, while cell viability stays preserved. Moreover, agmatine alone causes delayed Nrf2 nuclear overexpression and an increase in total glutathione content, eventually leading to an adaptive stress response. On the other hand, in Lps-stimulated microglia, agmatine prevents lipid peroxidation, readily upregulates the nuclear protein levels of Nrf2, which increases gene and protein expression of HO-1, and maintains delayed Nrf2 nuclear overexpression, resulting in increased total glutathione content associated with cytoprotection. Overall, we interpret agmatine-induced oxidative stress in non-activated microglia as triggering the adaptive response via Nrf2 and total glutathione, enabling them to cope with subsequent stressors, ie, Lps.
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  - Agmatine upregulates Nrf2/HO-1 pathway in Lps-stimulated microglia
SP  - 106
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5875
ER  - 

@conference{
author = "Milošević, Katarina and Milošević, Ana and Živković, Anica and Stevanović, Ivana and Laketa, Danijela and Božić, Iva and Janjić, Marija and Bjelobaba, Ivana and Lavrnja, Irena and Savić, Danijela",
year = "2023",
abstract = "Oxidative burst is a component of neuroinflammation whereby microglia-generated reactive oxygen species (ROS) either target pathogens or act as secondary messengers for microglial activation. In response to increased ROS during microglial activation, cytoprotective mechanisms are initiated primarily via Nrf2 activation and HO-1 expression. Agmatine is known to exert neuroprotective effect in vivo due to Nrf2 induction. While agmatine has been shown to activate the Nrf2/HO-1 signaling and protect macrophages from Lps-induced inflammation in vitro, its interaction with this pathway in activated microglia remains unexplored. Therefore, we sought to examine the potential of 100 μM agmatine as a pretreatment of Lps to activate Nrf2 in BV-2 microglia. In addition to cell viability, we analyzed the nuclear level of Nrf2 by Western blot and the expression of Hmox1 by PCR, as well as the protein level of HO-1. We also measured indicators of prooxidant and antioxidant activity: 4-HNE and total glutathione, respectively. Agmatine induces oxidative stress in non-stimulated microglia, as confirmed by the increase in the lipid peroxidation marker — 4-HNE, while cell viability stays preserved. Moreover, agmatine alone causes delayed Nrf2 nuclear overexpression and an increase in total glutathione content, eventually leading to an adaptive stress response. On the other hand, in Lps-stimulated microglia, agmatine prevents lipid peroxidation, readily upregulates the nuclear protein levels of Nrf2, which increases gene and protein expression of HO-1, and maintains delayed Nrf2 nuclear overexpression, resulting in increased total glutathione content associated with cytoprotection. Overall, we interpret agmatine-induced oxidative stress in non-activated microglia as triggering the adaptive response via Nrf2 and total glutathione, enabling them to cope with subsequent stressors, ie, Lps.",
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 = "Agmatine upregulates Nrf2/HO-1 pathway in Lps-stimulated microglia",
pages = "106",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5875"
}

Milošević, K., Milošević, A., Živković, A., Stevanović, I., Laketa, D., Božić, I., Janjić, M., Bjelobaba, I., Lavrnja, I.,& Savić, D.. (2023). Agmatine upregulates Nrf2/HO-1 pathway in Lps-stimulated microglia. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 106.
https://hdl.handle.net/21.15107/rcub_ibiss_5875

Milošević K, Milošević A, Živković A, Stevanović I, Laketa D, Božić I, Janjić M, Bjelobaba I, Lavrnja I, Savić D. Agmatine upregulates Nrf2/HO-1 pathway in Lps-stimulated microglia. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:106.
https://hdl.handle.net/21.15107/rcub_ibiss_5875 .

Milošević, Katarina, Milošević, Ana, Živković, Anica, Stevanović, Ivana, Laketa, Danijela, Božić, Iva, Janjić, Marija, Bjelobaba, Ivana, Lavrnja, Irena, Savić, Danijela, "Agmatine upregulates Nrf2/HO-1 pathway in Lps-stimulated microglia" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):106,
https://hdl.handle.net/21.15107/rcub_ibiss_5875 .

TY  - JOUR
AU  - Jeremić, Rada
AU  - Peković, Sanja
AU  - Lavrnja, Irena
AU  - Bjelobaba, Ivana
AU  - Đelić, Marina
AU  - Dacić, Sanja
AU  - Brkić, Predrag D
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5975
AB  - A growing body of evidence suggests that hyperbaric oxygenation (HBO) may affect the activity of adult neural stem cells (NSCs). Since the role of NSCs in recovery from brain injury is still unclear, the purpose of this study was to investigate the effects of sensorimotor cortex ablation (SCA) and HBO treatment (HBOT) on the processes of neurogenesis in the adult dentate gyrus (DG), a region of the hippocampus that is the site of adult neurogenesis. Ten-week-old Wistar rats were divided into groups: Control (C, intact animals), Sham control (S, animals that underwent the surgical procedure without opening the skull), SCA (animals in whom the right sensorimotor cortex was removed via suction ablation), and SCA + HBO (operated animals that passed HBOT). HBOT protocol: pressure applied at 2.5 absolute atmospheres for 60 min, once daily for 10 days. Using immunohistochemistry and double immunofluorescence labeling, we show that SCA causes significant loss of neurons in the DG. Newborn neurons in the subgranular zone (SGZ), inner-third, and partially mid-third of the granule cell layer are predominantly affected by SCA. HBOT decreases the SCA-caused loss of immature neurons, prevents reduction of dendritic arborization, and increases proliferation of progenitor cells. Our results suggest a protective effect of HBO by reducing the vulnerability of immature neurons in the adult DG to SCA injury.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Hyperbaric Oxygenation Prevents Loss of Immature Neurons in the Adult Hippocampal Dentate Gyrus Following Brain Injury
IS  - 5
VL  - 24
DO  - 10.3390/ijms24054261
SP  - 4261
ER  - 

@article{
author = "Jeremić, Rada and Peković, Sanja and Lavrnja, Irena and Bjelobaba, Ivana and Đelić, Marina and Dacić, Sanja and Brkić, Predrag D",
year = "2023",
abstract = "A growing body of evidence suggests that hyperbaric oxygenation (HBO) may affect the activity of adult neural stem cells (NSCs). Since the role of NSCs in recovery from brain injury is still unclear, the purpose of this study was to investigate the effects of sensorimotor cortex ablation (SCA) and HBO treatment (HBOT) on the processes of neurogenesis in the adult dentate gyrus (DG), a region of the hippocampus that is the site of adult neurogenesis. Ten-week-old Wistar rats were divided into groups: Control (C, intact animals), Sham control (S, animals that underwent the surgical procedure without opening the skull), SCA (animals in whom the right sensorimotor cortex was removed via suction ablation), and SCA + HBO (operated animals that passed HBOT). HBOT protocol: pressure applied at 2.5 absolute atmospheres for 60 min, once daily for 10 days. Using immunohistochemistry and double immunofluorescence labeling, we show that SCA causes significant loss of neurons in the DG. Newborn neurons in the subgranular zone (SGZ), inner-third, and partially mid-third of the granule cell layer are predominantly affected by SCA. HBOT decreases the SCA-caused loss of immature neurons, prevents reduction of dendritic arborization, and increases proliferation of progenitor cells. Our results suggest a protective effect of HBO by reducing the vulnerability of immature neurons in the adult DG to SCA injury.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Hyperbaric Oxygenation Prevents Loss of Immature Neurons in the Adult Hippocampal Dentate Gyrus Following Brain Injury",
number = "5",
volume = "24",
doi = "10.3390/ijms24054261",
pages = "4261"
}

Jeremić, R., Peković, S., Lavrnja, I., Bjelobaba, I., Đelić, M., Dacić, S.,& Brkić, P. D.. (2023). Hyperbaric Oxygenation Prevents Loss of Immature Neurons in the Adult Hippocampal Dentate Gyrus Following Brain Injury. in International Journal of Molecular Sciences
Basel: MDPI., 24(5), 4261.
https://doi.org/10.3390/ijms24054261

Jeremić R, Peković S, Lavrnja I, Bjelobaba I, Đelić M, Dacić S, Brkić PD. Hyperbaric Oxygenation Prevents Loss of Immature Neurons in the Adult Hippocampal Dentate Gyrus Following Brain Injury. in International Journal of Molecular Sciences. 2023;24(5):4261.
doi:10.3390/ijms24054261 .

Jeremić, Rada, Peković, Sanja, Lavrnja, Irena, Bjelobaba, Ivana, Đelić, Marina, Dacić, Sanja, Brkić, Predrag D, "Hyperbaric Oxygenation Prevents Loss of Immature Neurons in the Adult Hippocampal Dentate Gyrus Following Brain Injury" in International Journal of Molecular Sciences, 24, no. 5 (2023):4261,
https://doi.org/10.3390/ijms24054261 . .

TY  - CONF
AU  - Jeremić, Rada
AU  - Peković, Sanja
AU  - Lavrnja, Irena
AU  - Bjelobaba, Ivana
AU  - Đelić, Marina N
AU  - Brkić, Predrag D
AU  - Dacić, Sanja
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5984
AB  - Introduction: There is growing evidence that hyperbaric oxygenation (HBO) can affect adult neural stem cells (NSCs) activity. Because the role of NSCs in recovery from brain injury is still unclear, this study examined how ablation of the sensorimotor cortex (SCA) and HBO treatment (HBOT) affect the process of neurogenesis in the adult dentate gyrus (DG), a region of the hippocampus considered to be the site of adult neurogenesis. Material and methods: Ten-week-old Wistar rats were divided into groups: Control (C, intact animals), SCA (animals in which the right sensorimotor cortex was removed by suction ablation), and SCA+HBO (operated animals subjected to HBOT). HBOT protocol: pressure applied at 2.5 absolute atmospheres for 60 min, once daily for 10 days. The effects of HBOT were monitored by immunohistochemistry and double immunofluorescence labeling. In addition, the number of DCX+ cells was determined along the length of the SGZ in the inner and separately in the outer blade of the right dentate gyrus. Also, the total dendrite length was measured and the number of branching points, dendrite terminals, and segments were counted to quantify dendritic arborization in each neuron. Results: HBOT decreases SCA-induced loss of immature neurons, prevents reduction of dendritic branching, and increases proliferation of progenitor cells. Conclusion: Our results suggest a protective effect of HBOT by reducing the vulnerability of immature neurons in the adult DG to SCA injury.
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  - Hyperbaric oxygen prevents dendrite degeneration and loss of DCX-positive newborn immature neurons in the dentate gyrus after traumatic brain injury
SP  - 78
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5984
ER  - 

@conference{
author = "Jeremić, Rada and Peković, Sanja and Lavrnja, Irena and Bjelobaba, Ivana and Đelić, Marina N and Brkić, Predrag D and Dacić, Sanja",
year = "2023",
abstract = "Introduction: There is growing evidence that hyperbaric oxygenation (HBO) can affect adult neural stem cells (NSCs) activity. Because the role of NSCs in recovery from brain injury is still unclear, this study examined how ablation of the sensorimotor cortex (SCA) and HBO treatment (HBOT) affect the process of neurogenesis in the adult dentate gyrus (DG), a region of the hippocampus considered to be the site of adult neurogenesis. Material and methods: Ten-week-old Wistar rats were divided into groups: Control (C, intact animals), SCA (animals in which the right sensorimotor cortex was removed by suction ablation), and SCA+HBO (operated animals subjected to HBOT). HBOT protocol: pressure applied at 2.5 absolute atmospheres for 60 min, once daily for 10 days. The effects of HBOT were monitored by immunohistochemistry and double immunofluorescence labeling. In addition, the number of DCX+ cells was determined along the length of the SGZ in the inner and separately in the outer blade of the right dentate gyrus. Also, the total dendrite length was measured and the number of branching points, dendrite terminals, and segments were counted to quantify dendritic arborization in each neuron. Results: HBOT decreases SCA-induced loss of immature neurons, prevents reduction of dendritic branching, and increases proliferation of progenitor cells. Conclusion: Our results suggest a protective effect of HBOT by reducing the vulnerability of immature neurons in the adult DG to SCA injury.",
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 = "Hyperbaric oxygen prevents dendrite degeneration and loss of DCX-positive newborn immature neurons in the dentate gyrus after traumatic brain injury",
pages = "78",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5984"
}

Jeremić, R., Peković, S., Lavrnja, I., Bjelobaba, I., Đelić, M. N., Brkić, P. D.,& Dacić, S.. (2023). Hyperbaric oxygen prevents dendrite degeneration and loss of DCX-positive newborn immature neurons in the dentate gyrus after traumatic brain injury. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 78.
https://hdl.handle.net/21.15107/rcub_ibiss_5984

Jeremić R, Peković S, Lavrnja I, Bjelobaba I, Đelić MN, Brkić PD, Dacić S. Hyperbaric oxygen prevents dendrite degeneration and loss of DCX-positive newborn immature neurons in the dentate gyrus after traumatic brain injury. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:78.
https://hdl.handle.net/21.15107/rcub_ibiss_5984 .

Jeremić, Rada, Peković, Sanja, Lavrnja, Irena, Bjelobaba, Ivana, Đelić, Marina N, Brkić, Predrag D, Dacić, Sanja, "Hyperbaric oxygen prevents dendrite degeneration and loss of DCX-positive newborn immature neurons in the dentate gyrus after traumatic brain injury" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):78,
https://hdl.handle.net/21.15107/rcub_ibiss_5984 .

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  - CONF
AU  - Živković, Anica
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Milošević, Katarina
AU  - Božić, Iva
AU  - Trifunović, Svetlana
AU  - Savić, Danijela
AU  - Bjelobaba, Ivana
AU  - Lavrnja, Irena
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5859
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
system (CNS) that leads to severe neurological deficits. In past decades, numerous
studies have observed that anterior pituitary hormones play a pivotal role in regulation
of physiological immune response, as well as development and course of autoimmune
diseases.
Specifically, growth hormone (GH) and prolactin (PRL), peptide hormones
synthesized and secreted by the anterior pituitary, have been implicated in regulating
the immune system. Growth hormone secretion is positively regulated by the
hypothalamic growth hormone-releasing hormone (GHRH), while somatostatin (SST)
inhibits the release of GH.
Previous studies demonstrated that GHRH and GH are implicated in development of
experimental autoimmune encephalomyelitis (EAE), a representative animal model of
MS. Significantly higher PRL serum levels in MS patients were also reported.
We investigated spatiotemporal differences in GH and PRL levels in pituitaries from
EAE animals. Using immunolabeling and stereological methods we evaluated changes
in volume density of GH- and PRL-positive cells in pituitary gland of animals with
EAE compared to healthy controls. As we determined that there is no change in cell
volume density, we checked if there are any changes in gene expression of PRL, GH,
as well as GHRH and SST. Growth hormone and prolactin protein expression was
also measured in anterior pituitary. Our results show that, in addition to GH- and
PRL-positive cells volume density, there are no significant changes in gene and
protein expression in anterior pituitary during EAE.
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  - Growth hormone and prolactin gene expression and protein levels are not affected during EAE in rats
SP  - 105
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5859
ER  - 

@conference{
author = "Živković, Anica and Milošević, Ana and Janjić, Marija and Milošević, Katarina and Božić, Iva and Trifunović, Svetlana and Savić, Danijela and Bjelobaba, Ivana and Lavrnja, Irena",
year = "2023",
abstract = "Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
system (CNS) that leads to severe neurological deficits. In past decades, numerous
studies have observed that anterior pituitary hormones play a pivotal role in regulation
of physiological immune response, as well as development and course of autoimmune
diseases.
Specifically, growth hormone (GH) and prolactin (PRL), peptide hormones
synthesized and secreted by the anterior pituitary, have been implicated in regulating
the immune system. Growth hormone secretion is positively regulated by the
hypothalamic growth hormone-releasing hormone (GHRH), while somatostatin (SST)
inhibits the release of GH.
Previous studies demonstrated that GHRH and GH are implicated in development of
experimental autoimmune encephalomyelitis (EAE), a representative animal model of
MS. Significantly higher PRL serum levels in MS patients were also reported.
We investigated spatiotemporal differences in GH and PRL levels in pituitaries from
EAE animals. Using immunolabeling and stereological methods we evaluated changes
in volume density of GH- and PRL-positive cells in pituitary gland of animals with
EAE compared to healthy controls. As we determined that there is no change in cell
volume density, we checked if there are any changes in gene expression of PRL, GH,
as well as GHRH and SST. Growth hormone and prolactin protein expression was
also measured in anterior pituitary. Our results show that, in addition to GH- and
PRL-positive cells volume density, there are no significant changes in gene and
protein expression in anterior pituitary during EAE.",
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 = "Growth hormone and prolactin gene expression and protein levels are not affected during EAE in rats",
pages = "105",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5859"
}

Živković, A., Milošević, A., Janjić, M., Milošević, K., Božić, I., Trifunović, S., Savić, D., Bjelobaba, I.,& Lavrnja, I.. (2023). Growth hormone and prolactin gene expression and protein levels are not affected during EAE in rats. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 105.
https://hdl.handle.net/21.15107/rcub_ibiss_5859

Živković A, Milošević A, Janjić M, Milošević K, Božić I, Trifunović S, Savić D, Bjelobaba I, Lavrnja I. Growth hormone and prolactin gene expression and protein levels are not affected during EAE in rats. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:105.
https://hdl.handle.net/21.15107/rcub_ibiss_5859 .

Živković, Anica, Milošević, Ana, Janjić, Marija, Milošević, Katarina, Božić, Iva, Trifunović, Svetlana, Savić, Danijela, Bjelobaba, Ivana, Lavrnja, Irena, "Growth hormone and prolactin gene expression and protein levels are not affected during EAE in rats" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):105,
https://hdl.handle.net/21.15107/rcub_ibiss_5859 .

TY  - CONF
AU  - Milošević, Ana
AU  - Milošević, Katarina
AU  - Nikolić, Ljiljana
AU  - Bogdanović Pristov, Jelena
AU  - Božić, Iva
AU  - Živković, Anica
AU  - Lavrnja, Irena
AU  - Savić, Danijela
AU  - Janjić, Marija
AU  - Bjelobaba, Ivana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5836
AB  - Gonadotropin-releasing hormone (GnRH) is a hypothalamic decapeptide that controls
mammalian reproduction by acting on its receptor (GnRHR) expressed on pituitary
gonadotrope cells. While GnRHR signaling in gonadotropes is well described,
knowledge of GnRHR activation-related events at extrapituitary sites including
neurons is limited. It was proposed that GnRH analogs (GnRHa) induce distinct
changes in hippocampal gene expression, emotional processes, and cognitive
functions.
To explore neuronal GnRHR signaling we used the human neuroblastoma cell line
SH-SY5Y. Further, we explored the regional expression of Gnrhr in rat brain and
investigated the expression of several relevant genes in the hippocampus and preoptic
area of peripubertal male rats treated with GnRHa.
GNRHR is expressed in SH-SY5Y cell line, but its expression does not change after
adding GnRHa in the incubation media. Electrophysiological recordings confirmed
that GnRHa induced membrane depolarization but could not evoke action potentials.
In the rat brain, Gnrhr expression could be detected in the hippocampus, amygdala,
and hypothalamus, including the preoptic area. Prolonged treatment of peripubertal
rats with GnRHa had no effect on the expression of genes in the hippocampus
previously shown to be affected in the sheep model of delayed puberty.
These results imply that neuronal GnRHR is either differently coupled (not coupled
with Gq/11 protein), or that its membrane density is too low to induce transcriptional
events. More investigation is needed to elucidate the role(s) of GnRH-GnRHR
signaling in the brain.
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  - GnRHR signaling in neuronal cells: in vitro and in vivo data
SP  - 53
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5836
ER  - 

@conference{
author = "Milošević, Ana and Milošević, Katarina and Nikolić, Ljiljana and Bogdanović Pristov, Jelena and Božić, Iva and Živković, Anica and Lavrnja, Irena and Savić, Danijela and Janjić, Marija and Bjelobaba, Ivana",
year = "2023",
abstract = "Gonadotropin-releasing hormone (GnRH) is a hypothalamic decapeptide that controls
mammalian reproduction by acting on its receptor (GnRHR) expressed on pituitary
gonadotrope cells. While GnRHR signaling in gonadotropes is well described,
knowledge of GnRHR activation-related events at extrapituitary sites including
neurons is limited. It was proposed that GnRH analogs (GnRHa) induce distinct
changes in hippocampal gene expression, emotional processes, and cognitive
functions.
To explore neuronal GnRHR signaling we used the human neuroblastoma cell line
SH-SY5Y. Further, we explored the regional expression of Gnrhr in rat brain and
investigated the expression of several relevant genes in the hippocampus and preoptic
area of peripubertal male rats treated with GnRHa.
GNRHR is expressed in SH-SY5Y cell line, but its expression does not change after
adding GnRHa in the incubation media. Electrophysiological recordings confirmed
that GnRHa induced membrane depolarization but could not evoke action potentials.
In the rat brain, Gnrhr expression could be detected in the hippocampus, amygdala,
and hypothalamus, including the preoptic area. Prolonged treatment of peripubertal
rats with GnRHa had no effect on the expression of genes in the hippocampus
previously shown to be affected in the sheep model of delayed puberty.
These results imply that neuronal GnRHR is either differently coupled (not coupled
with Gq/11 protein), or that its membrane density is too low to induce transcriptional
events. More investigation is needed to elucidate the role(s) of GnRH-GnRHR
signaling in the brain.",
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 = "GnRHR signaling in neuronal cells: in vitro and in vivo data",
pages = "53",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5836"
}

Milošević, A., Milošević, K., Nikolić, L., Bogdanović Pristov, J., Božić, I., Živković, A., Lavrnja, I., Savić, D., Janjić, M.,& Bjelobaba, I.. (2023). GnRHR signaling in neuronal cells: in vitro and in vivo data. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 53.
https://hdl.handle.net/21.15107/rcub_ibiss_5836

Milošević A, Milošević K, Nikolić L, Bogdanović Pristov J, Božić I, Živković A, Lavrnja I, Savić D, Janjić M, Bjelobaba I. GnRHR signaling in neuronal cells: in vitro and in vivo data. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:53.
https://hdl.handle.net/21.15107/rcub_ibiss_5836 .

Milošević, Ana, Milošević, Katarina, Nikolić, Ljiljana, Bogdanović Pristov, Jelena, Božić, Iva, Živković, Anica, Lavrnja, Irena, Savić, Danijela, Janjić, Marija, Bjelobaba, Ivana, "GnRHR signaling in neuronal cells: in vitro and in vivo data" in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):53,
https://hdl.handle.net/21.15107/rcub_ibiss_5836 .

TY  - JOUR
AU  - Milošević, Ana
AU  - Lavrnja, Irena
AU  - Savić, Danijela
AU  - Milošević, Katarina
AU  - Skuljec, Jelena
AU  - Bjelobaba, Ivana
AU  - Janjić, Marija
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5757
AB  - Multiple sclerosis (MS) is an autoimmune disease affecting the CNS and occurring far more prevalently in women than in men. In both MS and its animal models, sex hormones play important immunomodulatory roles. We have previously shown that experimental autoimmune encephalomyelitis (EAE) affects the hypothalamic-pituitary-gonadal axis in rats of both sexes and induces an arrest in the estrous cycle in females. To investigate the gonadal status in female rats with EAE, we explored ovarian morphometric parameters, circulating and intraovarian sex steroid levels, and the expression of steroidogenic machinery components in the ovarian tissue. A prolonged state of diestrus was recorded during the peak of EAE, with maintenance of the corpora lutea, elevated intraovarian progesterone levels, and increased gene and protein expression of StAR, similar to the state of pseudopregnancy. The decrease in CYP17A1 protein expression was followed by a decrease in ovarian testosterone and estradiol levels. On the contrary, serum testosterone levels were slightly increased. With unchanged serum estradiol levels, these results point at extra-gonadal sites of sex steroid biosynthesis and catabolism as important regulators of their circulating levels. Our study suggests alterations in the function of the female reproductive system during central autoimmunity and highlights the bidirectional relationships between hormonal status and EAE.
PB  - Basel: MDPI
T2  - Cells
T1  - Rat Ovarian Function Is Impaired during Experimental Autoimmune Encephalomyelitis
IS  - 7
VL  - 12
DO  - 10.3390/cells12071045
SP  - 1054
ER  - 

@article{
author = "Milošević, Ana and Lavrnja, Irena and Savić, Danijela and Milošević, Katarina and Skuljec, Jelena and Bjelobaba, Ivana and Janjić, Marija",
year = "2023",
abstract = "Multiple sclerosis (MS) is an autoimmune disease affecting the CNS and occurring far more prevalently in women than in men. In both MS and its animal models, sex hormones play important immunomodulatory roles. We have previously shown that experimental autoimmune encephalomyelitis (EAE) affects the hypothalamic-pituitary-gonadal axis in rats of both sexes and induces an arrest in the estrous cycle in females. To investigate the gonadal status in female rats with EAE, we explored ovarian morphometric parameters, circulating and intraovarian sex steroid levels, and the expression of steroidogenic machinery components in the ovarian tissue. A prolonged state of diestrus was recorded during the peak of EAE, with maintenance of the corpora lutea, elevated intraovarian progesterone levels, and increased gene and protein expression of StAR, similar to the state of pseudopregnancy. The decrease in CYP17A1 protein expression was followed by a decrease in ovarian testosterone and estradiol levels. On the contrary, serum testosterone levels were slightly increased. With unchanged serum estradiol levels, these results point at extra-gonadal sites of sex steroid biosynthesis and catabolism as important regulators of their circulating levels. Our study suggests alterations in the function of the female reproductive system during central autoimmunity and highlights the bidirectional relationships between hormonal status and EAE.",
publisher = "Basel: MDPI",
journal = "Cells",
title = "Rat Ovarian Function Is Impaired during Experimental Autoimmune Encephalomyelitis",
number = "7",
volume = "12",
doi = "10.3390/cells12071045",
pages = "1054"
}

Milošević, A., Lavrnja, I., Savić, D., Milošević, K., Skuljec, J., Bjelobaba, I.,& Janjić, M.. (2023). Rat Ovarian Function Is Impaired during Experimental Autoimmune Encephalomyelitis. in Cells
Basel: MDPI., 12(7), 1054.
https://doi.org/10.3390/cells12071045

Milošević A, Lavrnja I, Savić D, Milošević K, Skuljec J, Bjelobaba I, Janjić M. Rat Ovarian Function Is Impaired during Experimental Autoimmune Encephalomyelitis. in Cells. 2023;12(7):1054.
doi:10.3390/cells12071045 .

Milošević, Ana, Lavrnja, Irena, Savić, Danijela, Milošević, Katarina, Skuljec, Jelena, Bjelobaba, Ivana, Janjić, Marija, "Rat Ovarian Function Is Impaired during Experimental Autoimmune Encephalomyelitis" in Cells, 12, no. 7 (2023):1054,
https://doi.org/10.3390/cells12071045 . .

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  - Milošević, Katarina
AU  - Stevanović, Ivana
AU  - Božić, Iva
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Laketa, Danijela
AU  - Bjelobaba, Ivana
AU  - Lavrnja, Irena
AU  - Savić, Danijela
PY  - 2022
UR  - https://www.mdpi.com/1422-0067/23/7/3561
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8998340
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4948
AB  - Neuroinflammation and microglial activation, common components of most neurodegenerative diseases, can be imitated in vitro by challenging microglia cells with Lps. We here aimed to evaluate the effects of agmatine pretreatment on Lps-induced oxidative stress in a mouse microglial BV-2 cell line. Our findings show that agmatine suppresses nitrosative and oxidative burst in Lps-stimulated microglia by reducing iNOS and XO activity and decreasing O2- levels, arresting lipid peroxidation, increasing total glutathione content, and preserving GR and CAT activity. In accordance with these results, agmatine suppresses inflammatory NF-kB, and stimulates antioxidant Nrf2 pathway, resulting in decreased TNF, IL-1 beta, and IL-6 release, and reduced iNOS and COX-2 levels. Together with increased ARG1, CD206 and HO-1 levels, our results imply that, in inflammatory conditions, agmatine pushes microglia towards an anti-inflammatory phenotype. Interestingly, we also discovered that agmatine alone increases lipid peroxidation end product levels, induces Nrf2 activation, increases total glutathione content, and GPx activity. Thus, we hypothesize that some of the effects of agmatine, observed in activated microglia, may be mediated by induced oxidative stress and adaptive response, prior to Lps stimulation.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Agmatine Mitigates Inflammation-Related Oxidative Stress in BV-2 Cells by Inducing a Pre-Adaptive Response.
IS  - 7
VL  - 23
DO  - 10.3390/ijms23073561
SP  - 3561
ER  - 

@article{
author = "Milošević, Katarina and Stevanović, Ivana and Božić, Iva and Milošević, Ana and Janjić, Marija and Laketa, Danijela and Bjelobaba, Ivana and Lavrnja, Irena and Savić, Danijela",
year = "2022",
abstract = "Neuroinflammation and microglial activation, common components of most neurodegenerative diseases, can be imitated in vitro by challenging microglia cells with Lps. We here aimed to evaluate the effects of agmatine pretreatment on Lps-induced oxidative stress in a mouse microglial BV-2 cell line. Our findings show that agmatine suppresses nitrosative and oxidative burst in Lps-stimulated microglia by reducing iNOS and XO activity and decreasing O2- levels, arresting lipid peroxidation, increasing total glutathione content, and preserving GR and CAT activity. In accordance with these results, agmatine suppresses inflammatory NF-kB, and stimulates antioxidant Nrf2 pathway, resulting in decreased TNF, IL-1 beta, and IL-6 release, and reduced iNOS and COX-2 levels. Together with increased ARG1, CD206 and HO-1 levels, our results imply that, in inflammatory conditions, agmatine pushes microglia towards an anti-inflammatory phenotype. Interestingly, we also discovered that agmatine alone increases lipid peroxidation end product levels, induces Nrf2 activation, increases total glutathione content, and GPx activity. Thus, we hypothesize that some of the effects of agmatine, observed in activated microglia, may be mediated by induced oxidative stress and adaptive response, prior to Lps stimulation.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Agmatine Mitigates Inflammation-Related Oxidative Stress in BV-2 Cells by Inducing a Pre-Adaptive Response.",
number = "7",
volume = "23",
doi = "10.3390/ijms23073561",
pages = "3561"
}

Milošević, K., Stevanović, I., Božić, I., Milošević, A., Janjić, M., Laketa, D., Bjelobaba, I., Lavrnja, I.,& Savić, D.. (2022). Agmatine Mitigates Inflammation-Related Oxidative Stress in BV-2 Cells by Inducing a Pre-Adaptive Response.. in International Journal of Molecular Sciences
Basel: MDPI., 23(7), 3561.
https://doi.org/10.3390/ijms23073561

Milošević K, Stevanović I, Božić I, Milošević A, Janjić M, Laketa D, Bjelobaba I, Lavrnja I, Savić D. Agmatine Mitigates Inflammation-Related Oxidative Stress in BV-2 Cells by Inducing a Pre-Adaptive Response.. in International Journal of Molecular Sciences. 2022;23(7):3561.
doi:10.3390/ijms23073561 .

Milošević, Katarina, Stevanović, Ivana, Božić, Iva, Milošević, Ana, Janjić, Marija, Laketa, Danijela, Bjelobaba, Ivana, Lavrnja, Irena, Savić, Danijela, "Agmatine Mitigates Inflammation-Related Oxidative Stress in BV-2 Cells by Inducing a Pre-Adaptive Response." in International Journal of Molecular Sciences, 23, no. 7 (2022):3561,
https://doi.org/10.3390/ijms23073561 . .

TY  - JOUR
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
AU  - Laketa, Danijela
PY  - 2022
UR  - https://doi.org/10.1007/s10571-021-01081-8
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4187
AB  - Dexamethasone (DEX) is frequently used to treat women at risk of preterm delivery, but although indispensable for the completion of organ maturation in the fetus, antenatal DEX treatment may exert adverse sex-dimorphic neurodevelopmental effects. Literature findings implicated oxidative stress in adverse effects of DEX treatment. Purinergic signaling is involved in neurodevelopment and controlled by ectonucleotidases, among which in the brain the most abundant are ectonucleoside triphosphate diphosphohydrolase 1 (NTPDase1/CD39) and ecto-5ʹ-nucleotidase (e5ʹNT/CD73), which jointly dephosphorylate ATP to adenosine. They are also involved in cell adhesion and migration, processes integral to brain development. Upregulation of CD39 and CD73 after DEX treatment was reported in adult rat hippocampus. We investigated the effects of maternal DEX treatment on CD39 and CD73 expression and enzymatic activity in the rat fetal brain of both sexes, in the context of oxidative status of the brain tissue. Fetuses were obtained at embryonic day (ED) 21, from Wistar rat dams treated with 0.5 mg DEX/kg/day, at ED 16, 17, and 18, and brains were processed and used for further analysis. Sex-specific increase in CD39 and CD73 expression and in the corresponding enzyme activities was induced in the brain of antenatally DEX-treated fetuses, more prominently in males. The oxidative stress induction after antenatal DEX treatment was confirmed in both sexes, although showing a slight bias in males. Due to the involvement of purinergic system in crucial neurodevelopmental processes, future investigations are needed to determine the role of these observed changes in the adverse effects of antenatal DEX treatment.
PB  - Springer
T2  - Cellular and Molecular Neurobiology
T1  - Antenatal Dexamethasone Treatment Induces Sex-dependent Upregulation of NTPDase1/CD39 and Ecto-5ʹ-nucleotidase/CD73 in the Rat Fetal Brain
VL  - 42
DO  - 10.1007/s10571-021-01081-8
SP  - 1965
EP  - 1981
ER  - 

@article{
author = "Manojlović-Stojanoski, Milica and Lavrnja, Irena and Stevanović, Ivana and Trifunović, Svetlana and Ristić, Nataša and Nestorović, Nataša and Sévigny, Jean and Nedeljković, Nadežda and Laketa, Danijela",
year = "2022",
abstract = "Dexamethasone (DEX) is frequently used to treat women at risk of preterm delivery, but although indispensable for the completion of organ maturation in the fetus, antenatal DEX treatment may exert adverse sex-dimorphic neurodevelopmental effects. Literature findings implicated oxidative stress in adverse effects of DEX treatment. Purinergic signaling is involved in neurodevelopment and controlled by ectonucleotidases, among which in the brain the most abundant are ectonucleoside triphosphate diphosphohydrolase 1 (NTPDase1/CD39) and ecto-5ʹ-nucleotidase (e5ʹNT/CD73), which jointly dephosphorylate ATP to adenosine. They are also involved in cell adhesion and migration, processes integral to brain development. Upregulation of CD39 and CD73 after DEX treatment was reported in adult rat hippocampus. We investigated the effects of maternal DEX treatment on CD39 and CD73 expression and enzymatic activity in the rat fetal brain of both sexes, in the context of oxidative status of the brain tissue. Fetuses were obtained at embryonic day (ED) 21, from Wistar rat dams treated with 0.5 mg DEX/kg/day, at ED 16, 17, and 18, and brains were processed and used for further analysis. Sex-specific increase in CD39 and CD73 expression and in the corresponding enzyme activities was induced in the brain of antenatally DEX-treated fetuses, more prominently in males. The oxidative stress induction after antenatal DEX treatment was confirmed in both sexes, although showing a slight bias in males. Due to the involvement of purinergic system in crucial neurodevelopmental processes, future investigations are needed to determine the role of these observed changes in the adverse effects of antenatal DEX treatment.",
publisher = "Springer",
journal = "Cellular and Molecular Neurobiology",
title = "Antenatal Dexamethasone Treatment Induces Sex-dependent Upregulation of NTPDase1/CD39 and Ecto-5ʹ-nucleotidase/CD73 in the Rat Fetal Brain",
volume = "42",
doi = "10.1007/s10571-021-01081-8",
pages = "1965-1981"
}

Manojlović-Stojanoski, M., Lavrnja, I., Stevanović, I., Trifunović, S., Ristić, N., Nestorović, N., Sévigny, J., Nedeljković, N.,& Laketa, D.. (2022). Antenatal Dexamethasone Treatment Induces Sex-dependent Upregulation of NTPDase1/CD39 and Ecto-5ʹ-nucleotidase/CD73 in the Rat Fetal Brain. in Cellular and Molecular Neurobiology
Springer., 42, 1965-1981.
https://doi.org/10.1007/s10571-021-01081-8

Manojlović-Stojanoski M, Lavrnja I, Stevanović I, Trifunović S, Ristić N, Nestorović N, Sévigny J, Nedeljković N, Laketa D. Antenatal Dexamethasone Treatment Induces Sex-dependent Upregulation of NTPDase1/CD39 and Ecto-5ʹ-nucleotidase/CD73 in the Rat Fetal Brain. in Cellular and Molecular Neurobiology. 2022;42:1965-1981.
doi:10.1007/s10571-021-01081-8 .

Manojlović-Stojanoski, Milica, Lavrnja, Irena, Stevanović, Ivana, Trifunović, Svetlana, Ristić, Nataša, Nestorović, Nataša, Sévigny, Jean, Nedeljković, Nadežda, Laketa, Danijela, "Antenatal Dexamethasone Treatment Induces Sex-dependent Upregulation of NTPDase1/CD39 and Ecto-5ʹ-nucleotidase/CD73 in the Rat Fetal Brain" in Cellular and Molecular Neurobiology, 42 (2022):1965-1981,
https://doi.org/10.1007/s10571-021-01081-8 . .

TY  - CONF
AU  - Milošević, Katarina
AU  - Stevanović, Ivana
AU  - Božić, Iva
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Laketa, Danijela
AU  - Bjelobaba, Ivana
AU  - Lavrnja, Irena
AU  - Savić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5749
AB  - Prekomerna neuroinflamacija i mikroglijska aktivacija su uključene u patologiju mnogih neurodegenerativnih bolesti i mogu se simulirati u in vitro sistemu mikroglijskih ćelija primenom bakterijskog lipolisaharida (engl. Lipopolisaharide, LPS). Naša studija imala je za cilj da proceni efekte  pretretmana agmatinom na LPS-om izazvani oksidativni stres u BV-2 mišjoj mikroglijskoj ćelijskoj liniji. Pokazano je da u LPS-om stimulisanoj mikrogliji agmatin smanjuje enzimsku aktivnost iNOS i ksantin oksidaze (engl. Xanthine oxidase, XO), kao i nivo O2−, zaustavlja lipidnu peroksidaciju, povećava količinu ukupnog glutationa i omogućava da se delimično očuva aktivnost glutation reduktaze i katalaze, čime redukuje azotni i oksidativni stres. Agmatin utiče i na dva glavna signalna puta (NF-kB i Nrf2) uključena u inflamaciju, odnosno, antioksidativnu zaštitu, smanjujući tako nivo iNOS i COX-2, kao i oslobađanje TNF, IL-1β i IL-6. Istovremeno povećava se nivo ARG1, CD206 i HO-1, iz čega proizilazi da u uslovima inflamacije agmatin moduliše aktivaciju mikroglije u pravcu antiinflamacijskog fenotipa. Pokazali smo i da sam agmatin kod BV-2 ćelija dovodi do porasta nivoa krajnjih produkata lipidne peroksidacije, ali i ukupnog glutationa, aktivnosti glutation peroksidaze i aktivacije Nrf2 puta. Ovi rezultati podržavaju hipotezu da su agmatinom izazvani oksidativni stres i adaptivni odgovor, koji prethode stimulaciji LPS-om, odgovorni za efekte agmatina u aktiviranoj mikrogliji.
AB  - Прекомерена неуроинфламација и микроглијска активација су укључене у
патологију многих неуродегенеративних болести и могу се симулирати у in vitro
систему микроглијских ћелија применом бактеријског липолисахарида (енгл.
Lipopolisaharide, LPS). Наша студија имала је за циљ да процени ефекте
претретмана агматином на LPS-ом изазвани оксидативни стрес у BV-2 мишјој
микроглијској ћелијској линији. Показано је да у LPS-ом стимулисаној микроглији
агматин смањује ензимску активност iNOS и ксантин оксидазе (енгл. Xanthine
oxidase, XO), као и ниво O2−, зауставља липидну пероксидацију, повећава количину
укупног глутатиона и омогућава да се делимично очува активност глутатион
редуктазе и каталазе, чиме редукује азотни и оксидативни стрес. Агматин утиче и
на два главна сигнална пута (NF-kB и Nrf2) укључена у инфламацију, односно,
антиоксидативну заштиту, смањујући тако ниво iNOS и COX-2, као и ослобађање
TNF, IL-1β и IL-6. Истовремено повећава се ниво ARG1, CD206 и HO-1, из чега
произилази да у условима инфламације агматин модулише активацију микроглије
у правцу антиинфламацијског фенотипа. Показали смо и да сам агматин код BV-2
ћелија доводи до пораста нивоа крајњих продуката липидне пероксидације, али и
укупног глутатиона, активности глутатион пероксидазе и активације Nrf2 пута.
Ови резултати подржавају хипотезу да су агматином изазвани оксидативни стрес и
адаптивни одговор, који претходе стимулацији LPS-ом, одговорни за ефекте
агматина у активираној микроглији.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Uticaj agmatina na oksidativni i inflamacijski odgovor mikroglijskih ćelija aktiviranih bakterijskim lipopolisaharidom
T1  - Утицај агматина на оксидативни и инфламацијски одговор микроглијских ћелија активираних бактеријским липополисахаридом
SP  - 290
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5749
ER  - 

@conference{
author = "Milošević, Katarina and Stevanović, Ivana and Božić, Iva and Milošević, Ana and Janjić, Marija and Laketa, Danijela and Bjelobaba, Ivana and Lavrnja, Irena and Savić, Danijela",
year = "2022",
abstract = "Prekomerna neuroinflamacija i mikroglijska aktivacija su uključene u patologiju mnogih neurodegenerativnih bolesti i mogu se simulirati u in vitro sistemu mikroglijskih ćelija primenom bakterijskog lipolisaharida (engl. Lipopolisaharide, LPS). Naša studija imala je za cilj da proceni efekte  pretretmana agmatinom na LPS-om izazvani oksidativni stres u BV-2 mišjoj mikroglijskoj ćelijskoj liniji. Pokazano je da u LPS-om stimulisanoj mikrogliji agmatin smanjuje enzimsku aktivnost iNOS i ksantin oksidaze (engl. Xanthine oxidase, XO), kao i nivo O2−, zaustavlja lipidnu peroksidaciju, povećava količinu ukupnog glutationa i omogućava da se delimično očuva aktivnost glutation reduktaze i katalaze, čime redukuje azotni i oksidativni stres. Agmatin utiče i na dva glavna signalna puta (NF-kB i Nrf2) uključena u inflamaciju, odnosno, antioksidativnu zaštitu, smanjujući tako nivo iNOS i COX-2, kao i oslobađanje TNF, IL-1β i IL-6. Istovremeno povećava se nivo ARG1, CD206 i HO-1, iz čega proizilazi da u uslovima inflamacije agmatin moduliše aktivaciju mikroglije u pravcu antiinflamacijskog fenotipa. Pokazali smo i da sam agmatin kod BV-2 ćelija dovodi do porasta nivoa krajnjih produkata lipidne peroksidacije, ali i ukupnog glutationa, aktivnosti glutation peroksidaze i aktivacije Nrf2 puta. Ovi rezultati podržavaju hipotezu da su agmatinom izazvani oksidativni stres i adaptivni odgovor, koji prethode stimulaciji LPS-om, odgovorni za efekte agmatina u aktiviranoj mikrogliji., Прекомерена неуроинфламација и микроглијска активација су укључене у
патологију многих неуродегенеративних болести и могу се симулирати у in vitro
систему микроглијских ћелија применом бактеријског липолисахарида (енгл.
Lipopolisaharide, LPS). Наша студија имала је за циљ да процени ефекте
претретмана агматином на LPS-ом изазвани оксидативни стрес у BV-2 мишјој
микроглијској ћелијској линији. Показано је да у LPS-ом стимулисаној микроглији
агматин смањује ензимску активност iNOS и ксантин оксидазе (енгл. Xanthine
oxidase, XO), као и ниво O2−, зауставља липидну пероксидацију, повећава количину
укупног глутатиона и омогућава да се делимично очува активност глутатион
редуктазе и каталазе, чиме редукује азотни и оксидативни стрес. Агматин утиче и
на два главна сигнална пута (NF-kB и Nrf2) укључена у инфламацију, односно,
антиоксидативну заштиту, смањујући тако ниво iNOS и COX-2, као и ослобађање
TNF, IL-1β и IL-6. Истовремено повећава се ниво ARG1, CD206 и HO-1, из чега
произилази да у условима инфламације агматин модулише активацију микроглије
у правцу антиинфламацијског фенотипа. Показали смо и да сам агматин код BV-2
ћелија доводи до пораста нивоа крајњих продуката липидне пероксидације, али и
укупног глутатиона, активности глутатион пероксидазе и активације Nrf2 пута.
Ови резултати подржавају хипотезу да су агматином изазвани оксидативни стрес и
адаптивни одговор, који претходе стимулацији LPS-ом, одговорни за ефекте
агматина у активираној микроглији.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Uticaj agmatina na oksidativni i inflamacijski odgovor mikroglijskih ćelija aktiviranih bakterijskim lipopolisaharidom, Утицај агматина на оксидативни и инфламацијски одговор микроглијских ћелија активираних бактеријским липополисахаридом",
pages = "290",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5749"
}

Milošević, K., Stevanović, I., Božić, I., Milošević, A., Janjić, M., Laketa, D., Bjelobaba, I., Lavrnja, I.,& Savić, D.. (2022). Uticaj agmatina na oksidativni i inflamacijski odgovor mikroglijskih ćelija aktiviranih bakterijskim lipopolisaharidom. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 290.
https://hdl.handle.net/21.15107/rcub_ibiss_5749

Milošević K, Stevanović I, Božić I, Milošević A, Janjić M, Laketa D, Bjelobaba I, Lavrnja I, Savić D. Uticaj agmatina na oksidativni i inflamacijski odgovor mikroglijskih ćelija aktiviranih bakterijskim lipopolisaharidom. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:290.
https://hdl.handle.net/21.15107/rcub_ibiss_5749 .

Milošević, Katarina, Stevanović, Ivana, Božić, Iva, Milošević, Ana, Janjić, Marija, Laketa, Danijela, Bjelobaba, Ivana, Lavrnja, Irena, Savić, Danijela, "Uticaj agmatina na oksidativni i inflamacijski odgovor mikroglijskih ćelija aktiviranih bakterijskim lipopolisaharidom" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):290,
https://hdl.handle.net/21.15107/rcub_ibiss_5749 .

TY  - CONF
AU  - Manojlović-Stojanoski, Milica
AU  - Lavrnja, Irena
AU  - Stevanović, Ivana
AU  - Trifunović, Svetlana
AU  - Ristić, Nataša
AU  - Nestorović, Nataša
AU  - Nedeljković, Nadežda
AU  - Laketa, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5750
AB  - Kod prevremeno rođene dece, nedovoljna izloženost endogenim glukokortikoidima vodi često do fatalnih komplikacija, koje mogu biti sprečene antenatalnim tretmanom sintetskim glukokortikoidima, najčešće deksametazonom (DEKS). Prema važećim preporukama, trudnice u riziku od prevremenog porođaja između 24-te i 34-te nedelje trudnoće treba da prime jedan tretman deksametazonom. I pored rizika od neželjenih neurorazvojnih efekata, često se primenjuje ponavljani tretman. Purinski signalni sistem ima važnu ulogu u razviću mozga, a ključnu ulogu imaju najzastupljenije ektonukleotidaze NTPDaza1/CD39 i ekto-5ʹ-nukleotidaza/CD73 koje zajednički regulišu nivo ATP, ADP i adenozina u vanćelijskoj tečnosti. Mi smo primenili antenatalni ponavljani tretman deksametazonom (APTD) 15, 16 i 17 dana gestacije (DG) kod trudnih ženki Wistar pacova. Fetusi su dobijeni 21. DG, a nakon dekapitacije izolovan je mozak koji je po uklanjanju cerebellum-a korišćen za dobijanje grube membranske frakcije, iRNK ili pripremljen za imunohistohemijsku analizu. Naši rezultati pokazuju da APTD izaziva porast genske i proteinske ekspresije, kao i enzimske aktivnosti NTPDaze1/CD39 i ekto-5ʹ-nukleotidaze/CD73 u mozgu fetusa kod pacova, koji je izraženiji kod muškog pola. Uočene promene ukazuju da APTD verovatno izaziva smanjenje ATP- i ADP-zavisne, a porast adenozinske signalizacije, izraženije u mozgu muških fetusa što bi moglo da doprinosi neželjenim neurorazvojnim efektima APTD, posebno kod muškog pola.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Ponavljani antenatalni tretman deksametazonom izaziva polno-zavisni porast ekspresije glavnih ektonukleotidaza u mozgu fetusa kod pacova
T1  - Понављани антенатални третман дексаметазоном изазива полно-зависни пораст експресије главних ектонуклеотидаза у мозгу фетуса код пацова
SP  - 351
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5750
ER  - 

@conference{
author = "Manojlović-Stojanoski, Milica and Lavrnja, Irena and Stevanović, Ivana and Trifunović, Svetlana and Ristić, Nataša and Nestorović, Nataša and Nedeljković, Nadežda and Laketa, Danijela",
year = "2022",
abstract = "Kod prevremeno rođene dece, nedovoljna izloženost endogenim glukokortikoidima vodi često do fatalnih komplikacija, koje mogu biti sprečene antenatalnim tretmanom sintetskim glukokortikoidima, najčešće deksametazonom (DEKS). Prema važećim preporukama, trudnice u riziku od prevremenog porođaja između 24-te i 34-te nedelje trudnoće treba da prime jedan tretman deksametazonom. I pored rizika od neželjenih neurorazvojnih efekata, često se primenjuje ponavljani tretman. Purinski signalni sistem ima važnu ulogu u razviću mozga, a ključnu ulogu imaju najzastupljenije ektonukleotidaze NTPDaza1/CD39 i ekto-5ʹ-nukleotidaza/CD73 koje zajednički regulišu nivo ATP, ADP i adenozina u vanćelijskoj tečnosti. Mi smo primenili antenatalni ponavljani tretman deksametazonom (APTD) 15, 16 i 17 dana gestacije (DG) kod trudnih ženki Wistar pacova. Fetusi su dobijeni 21. DG, a nakon dekapitacije izolovan je mozak koji je po uklanjanju cerebellum-a korišćen za dobijanje grube membranske frakcije, iRNK ili pripremljen za imunohistohemijsku analizu. Naši rezultati pokazuju da APTD izaziva porast genske i proteinske ekspresije, kao i enzimske aktivnosti NTPDaze1/CD39 i ekto-5ʹ-nukleotidaze/CD73 u mozgu fetusa kod pacova, koji je izraženiji kod muškog pola. Uočene promene ukazuju da APTD verovatno izaziva smanjenje ATP- i ADP-zavisne, a porast adenozinske signalizacije, izraženije u mozgu muških fetusa što bi moglo da doprinosi neželjenim neurorazvojnim efektima APTD, posebno kod muškog pola.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Ponavljani antenatalni tretman deksametazonom izaziva polno-zavisni porast ekspresije glavnih ektonukleotidaza u mozgu fetusa kod pacova, Понављани антенатални третман дексаметазоном изазива полно-зависни пораст експресије главних ектонуклеотидаза у мозгу фетуса код пацова",
pages = "351",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5750"
}

Manojlović-Stojanoski, M., Lavrnja, I., Stevanović, I., Trifunović, S., Ristić, N., Nestorović, N., Nedeljković, N.,& Laketa, D.. (2022). Ponavljani antenatalni tretman deksametazonom izaziva polno-zavisni porast ekspresije glavnih ektonukleotidaza u mozgu fetusa kod pacova. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 351.
https://hdl.handle.net/21.15107/rcub_ibiss_5750

Manojlović-Stojanoski M, Lavrnja I, Stevanović I, Trifunović S, Ristić N, Nestorović N, Nedeljković N, Laketa D. Ponavljani antenatalni tretman deksametazonom izaziva polno-zavisni porast ekspresije glavnih ektonukleotidaza u mozgu fetusa kod pacova. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:351.
https://hdl.handle.net/21.15107/rcub_ibiss_5750 .

Manojlović-Stojanoski, Milica, Lavrnja, Irena, Stevanović, Ivana, Trifunović, Svetlana, Ristić, Nataša, Nestorović, Nataša, Nedeljković, Nadežda, Laketa, Danijela, "Ponavljani antenatalni tretman deksametazonom izaziva polno-zavisni porast ekspresije glavnih ektonukleotidaza u mozgu fetusa kod pacova" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):351,
https://hdl.handle.net/21.15107/rcub_ibiss_5750 .

TY  - JOUR
AU  - Nikolovski, Neda
AU  - Božić, Iva
AU  - Miljković, Đorđe
AU  - Lavrnja, Irena
PY  - 2021
UR  - https://www.eurekaselect.com/185602/article
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4477
AB  - BACKGROUND Benfotiamine is a synthetic liposoluble derivative of vitamin B1 that has been shown to have anti-inflammatory properties. OBJECTIVE To study the effects of benfotiamine on dendritic cells. METHODS Dendritic cells were obtained from murine bone marrow precursor cells in the presence of GM-CSF. Benfotiamine was applied to the cell culture during the process of bone marrow cell differentiation into dendritic cells. Dendritic cells were stimulated with lipopolysaccharide (LPS) and expression of MHC class II molecules and CD86 was determined by flow cytometry, while levels of tumor necrosis factor (TNF) and interleukin (IL)-1β in cell culture supernatants were measured by ELISA. F-Actin, NF-κB and Nrf2 were visualized by immunofluorescent staining and microscopy. RESULTS Benfotiamine potently reduced LPS-induced expression of MHC class II molecules and CD86, in addition to suppressing the release of pro-inflammatory cytokines TNF and IL-1β. It also prevented LPS-imposed morphological changes of dendritic cells, i.e. enlargement and intensified protrusions. The effects were paralleled with the reduction of NF-κB translocation to the nucleus, but not of Nrf2 activation inhibition. CONCLUSION Having in mind the importance of dendritic cells for the configuration of the immune response, our results imply that benfotiamine has the ability to regulate the immune response through inhibition of inflammatory properties of dendritic cells.
T2  - Endocrine, Metabolic & Immune Disorders - Drug Targets
T1  - Benfotiamine Reduces Dendritic Cell Inflammatory Potency.
IS  - 7
VL  - 21
DO  - 10.2174/1871530320999200905114135
SP  - 1344
EP  - 1351
ER  - 

@article{
author = "Nikolovski, Neda and Božić, Iva and Miljković, Đorđe and Lavrnja, Irena",
year = "2021",
abstract = "BACKGROUND Benfotiamine is a synthetic liposoluble derivative of vitamin B1 that has been shown to have anti-inflammatory properties. OBJECTIVE To study the effects of benfotiamine on dendritic cells. METHODS Dendritic cells were obtained from murine bone marrow precursor cells in the presence of GM-CSF. Benfotiamine was applied to the cell culture during the process of bone marrow cell differentiation into dendritic cells. Dendritic cells were stimulated with lipopolysaccharide (LPS) and expression of MHC class II molecules and CD86 was determined by flow cytometry, while levels of tumor necrosis factor (TNF) and interleukin (IL)-1β in cell culture supernatants were measured by ELISA. F-Actin, NF-κB and Nrf2 were visualized by immunofluorescent staining and microscopy. RESULTS Benfotiamine potently reduced LPS-induced expression of MHC class II molecules and CD86, in addition to suppressing the release of pro-inflammatory cytokines TNF and IL-1β. It also prevented LPS-imposed morphological changes of dendritic cells, i.e. enlargement and intensified protrusions. The effects were paralleled with the reduction of NF-κB translocation to the nucleus, but not of Nrf2 activation inhibition. CONCLUSION Having in mind the importance of dendritic cells for the configuration of the immune response, our results imply that benfotiamine has the ability to regulate the immune response through inhibition of inflammatory properties of dendritic cells.",
journal = "Endocrine, Metabolic & Immune Disorders - Drug Targets",
title = "Benfotiamine Reduces Dendritic Cell Inflammatory Potency.",
number = "7",
volume = "21",
doi = "10.2174/1871530320999200905114135",
pages = "1344-1351"
}

Nikolovski, N., Božić, I., Miljković, Đ.,& Lavrnja, I.. (2021). Benfotiamine Reduces Dendritic Cell Inflammatory Potency.. in Endocrine, Metabolic & Immune Disorders - Drug Targets, 21(7), 1344-1351.
https://doi.org/10.2174/1871530320999200905114135

Nikolovski N, Božić I, Miljković Đ, Lavrnja I. Benfotiamine Reduces Dendritic Cell Inflammatory Potency.. in Endocrine, Metabolic & Immune Disorders - Drug Targets. 2021;21(7):1344-1351.
doi:10.2174/1871530320999200905114135 .

Nikolovski, Neda, Božić, Iva, Miljković, Đorđe, Lavrnja, Irena, "Benfotiamine Reduces Dendritic Cell Inflammatory Potency." in Endocrine, Metabolic & Immune Disorders - Drug Targets, 21, no. 7 (2021):1344-1351,
https://doi.org/10.2174/1871530320999200905114135 . .

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  - Milošević, Katarina
AU  - Stevanović, Ivana
AU  - Božić, Iva
AU  - Milošević, Ana
AU  - Jakovljević, Marija
AU  - Janjić, Marija
AU  - Bjelobaba, Ivana
AU  - Laketa, Danijela
AU  - Lavrnja, Irena
AU  - Savić, Danijela
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6003
AB  - Mitochondria play a key role in energy metabolism and regulate some of the principal cellular processes such as the production of ATP and reactive oxygen species, as well as a regulation of apoptotic cell death. Mitochondrial dysfunction and oxidative stress are common threads in most neurodegenerative disorders, which are also accompanied by chronic microglial activation. Agmatine, neuromodulatory polyamine, was shown to exhibit neuroprotective effects in oxidative stress conditions. Therefore, the goal of this study was to determine the ability of agmatine to preserve mitochondrial function and prevent apoptosis during neuroinflammation.
The effects of 100 µM agmatine on cellular energy status and cell death were examined in LPS-stimulated BV2 microglial cell line. To detect changes in mitochondrial membrane potential, TMRE fluorescent assay was performed, while the changes in intracellular ATP concentration were determined by bioluminescent assay, 6h, and 24h after LPS stimulation. The expression of apoptosis regulators Bax and Bcl2 was assessed by Western blot analysis and the Bax/Bcl2 ratio was determined.
Agmatine increases mitochondrial membrane potential, indicating its protective role during mitochondrial insult caused by LPS stimulation. LPS and agmatine administrated separately, increase intracellular ATP levels, however, agmatine treatment followed by LPS stimulation enhances ATP production even further, at both time points. Moreover, agmatine shows an antiapoptotic effect by reduction of Bax/Bcl2 ratio in comparison to LPS stimulation.
We conclude that the results of this study indicate the capacity of agmatine to protect mitochondrial function and suppress apoptosis, which may be beneficial in neurodegenerative disorders and
neuroinflammation.
PB  - Federation of European Neuroscience Societies
C3  - Book of Abstracts: Virtual FENS Regional Meeting 2021; 2021 Aug 25-27; Krakow, Poland
T1  - Agmatine protects mitochondria in LPS-stimulated microglia
SP  - 285
EP  - 286
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6003
ER  - 

@conference{
author = "Milošević, Katarina and Stevanović, Ivana and Božić, Iva and Milošević, Ana and Jakovljević, Marija and Janjić, Marija and Bjelobaba, Ivana and Laketa, Danijela and Lavrnja, Irena and Savić, Danijela",
year = "2021",
abstract = "Mitochondria play a key role in energy metabolism and regulate some of the principal cellular processes such as the production of ATP and reactive oxygen species, as well as a regulation of apoptotic cell death. Mitochondrial dysfunction and oxidative stress are common threads in most neurodegenerative disorders, which are also accompanied by chronic microglial activation. Agmatine, neuromodulatory polyamine, was shown to exhibit neuroprotective effects in oxidative stress conditions. Therefore, the goal of this study was to determine the ability of agmatine to preserve mitochondrial function and prevent apoptosis during neuroinflammation.
The effects of 100 µM agmatine on cellular energy status and cell death were examined in LPS-stimulated BV2 microglial cell line. To detect changes in mitochondrial membrane potential, TMRE fluorescent assay was performed, while the changes in intracellular ATP concentration were determined by bioluminescent assay, 6h, and 24h after LPS stimulation. The expression of apoptosis regulators Bax and Bcl2 was assessed by Western blot analysis and the Bax/Bcl2 ratio was determined.
Agmatine increases mitochondrial membrane potential, indicating its protective role during mitochondrial insult caused by LPS stimulation. LPS and agmatine administrated separately, increase intracellular ATP levels, however, agmatine treatment followed by LPS stimulation enhances ATP production even further, at both time points. Moreover, agmatine shows an antiapoptotic effect by reduction of Bax/Bcl2 ratio in comparison to LPS stimulation.
We conclude that the results of this study indicate the capacity of agmatine to protect mitochondrial function and suppress apoptosis, which may be beneficial in neurodegenerative disorders and
neuroinflammation.",
publisher = "Federation of European Neuroscience Societies",
journal = "Book of Abstracts: Virtual FENS Regional Meeting 2021; 2021 Aug 25-27; Krakow, Poland",
title = "Agmatine protects mitochondria in LPS-stimulated microglia",
pages = "285-286",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6003"
}

Milošević, K., Stevanović, I., Božić, I., Milošević, A., Jakovljević, M., Janjić, M., Bjelobaba, I., Laketa, D., Lavrnja, I.,& Savić, D.. (2021). Agmatine protects mitochondria in LPS-stimulated microglia. in Book of Abstracts: Virtual FENS Regional Meeting 2021; 2021 Aug 25-27; Krakow, Poland
Federation of European Neuroscience Societies., 285-286.
https://hdl.handle.net/21.15107/rcub_ibiss_6003

Milošević K, Stevanović I, Božić I, Milošević A, Jakovljević M, Janjić M, Bjelobaba I, Laketa D, Lavrnja I, Savić D. Agmatine protects mitochondria in LPS-stimulated microglia. in Book of Abstracts: Virtual FENS Regional Meeting 2021; 2021 Aug 25-27; Krakow, Poland. 2021;:285-286.
https://hdl.handle.net/21.15107/rcub_ibiss_6003 .

Milošević, Katarina, Stevanović, Ivana, Božić, Iva, Milošević, Ana, Jakovljević, Marija, Janjić, Marija, Bjelobaba, Ivana, Laketa, Danijela, Lavrnja, Irena, Savić, Danijela, "Agmatine protects mitochondria in LPS-stimulated microglia" in Book of Abstracts: Virtual FENS Regional Meeting 2021; 2021 Aug 25-27; Krakow, Poland (2021):285-286,
https://hdl.handle.net/21.15107/rcub_ibiss_6003 .

TY  - JOUR
AU  - Dejanović, Bratislav
AU  - Begović-Kuprešanin, Vesna
AU  - Stevanović, Ivana
AU  - Lavrnja, Irena
AU  - Šošić-Jurjević, Branka 
AU  - Ninković, Milica
AU  - Trifunović, Svetlana
PY  - 2021
UR  - http://www.doiserbia.nb.rs/Article.aspx?ID=0354-46642100028D
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4651
UR  - https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/6557
AB  - The use of the antidepressant drug chlorpromazine (CPZ) is linked to the occurrence of oxidative stress in some brain structures. Thus, overcoming the side effects of CPZ is of great importance. Because agmatine (AGM) can act as a free radical scavenger, it is an interesting compound as an adjunct to CPZ therapy. The aim of our study was to investigate the enzymatic parameters of oxidative stress in the hippocampus and striatum of rats after CPZ treatment, and the potential protective effects of AGM. Rats were injected as follows with (i) 1 mL/kg b.w. saline; (ii) a single intraperitoneal (i.p.) dose of CPZ (38.7 mg/kg); (iii) CPZ (38.7 mg/kg) and AGM (75 mg/kg); (iv) AGM (75 mg/kg). CPZ induced an increase in superoxide anion radical (O2 catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), were lowered in both the hippocampus striatum. Cotreatment with CPZ and AGM protected the examined brain structures by reversing the antioxidant enzyme control values. Following CPZ treatment, the effects were more pronounced for SOD and GPx in the hippocampus, the striatum. The full effect of restored superoxide production was achieved in the striatum, which points to the role of CAT. The obtained results suggest that CPZ in combination with AGM may be considered as a new treatment strategy.
PB  - Belgrade: Serbian Biological Society
T2  - Archives of Biological Sciences
T1  - Agmatine reduces chlorpromazine prooxidant effects in rat hippocampus and striatum
IS  - 3
VL  - 73
DO  - 10.2298/abs210429028d
SP  - 353
EP  - 359
ER  - 

@article{
author = "Dejanović, Bratislav and Begović-Kuprešanin, Vesna and Stevanović, Ivana and Lavrnja, Irena and Šošić-Jurjević, Branka  and Ninković, Milica and Trifunović, Svetlana",
year = "2021",
abstract = "The use of the antidepressant drug chlorpromazine (CPZ) is linked to the occurrence of oxidative stress in some brain structures. Thus, overcoming the side effects of CPZ is of great importance. Because agmatine (AGM) can act as a free radical scavenger, it is an interesting compound as an adjunct to CPZ therapy. The aim of our study was to investigate the enzymatic parameters of oxidative stress in the hippocampus and striatum of rats after CPZ treatment, and the potential protective effects of AGM. Rats were injected as follows with (i) 1 mL/kg b.w. saline; (ii) a single intraperitoneal (i.p.) dose of CPZ (38.7 mg/kg); (iii) CPZ (38.7 mg/kg) and AGM (75 mg/kg); (iv) AGM (75 mg/kg). CPZ induced an increase in superoxide anion radical (O2 catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), were lowered in both the hippocampus striatum. Cotreatment with CPZ and AGM protected the examined brain structures by reversing the antioxidant enzyme control values. Following CPZ treatment, the effects were more pronounced for SOD and GPx in the hippocampus, the striatum. The full effect of restored superoxide production was achieved in the striatum, which points to the role of CAT. The obtained results suggest that CPZ in combination with AGM may be considered as a new treatment strategy.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Archives of Biological Sciences",
title = "Agmatine reduces chlorpromazine prooxidant effects in rat hippocampus and striatum",
number = "3",
volume = "73",
doi = "10.2298/abs210429028d",
pages = "353-359"
}

Dejanović, B., Begović-Kuprešanin, V., Stevanović, I., Lavrnja, I., Šošić-Jurjević, B., Ninković, M.,& Trifunović, S.. (2021). Agmatine reduces chlorpromazine prooxidant effects in rat hippocampus and striatum. in Archives of Biological Sciences
Belgrade: Serbian Biological Society., 73(3), 353-359.
https://doi.org/10.2298/abs210429028d

Dejanović B, Begović-Kuprešanin V, Stevanović I, Lavrnja I, Šošić-Jurjević B, Ninković M, Trifunović S. Agmatine reduces chlorpromazine prooxidant effects in rat hippocampus and striatum. in Archives of Biological Sciences. 2021;73(3):353-359.
doi:10.2298/abs210429028d .

Dejanović, Bratislav, Begović-Kuprešanin, Vesna, Stevanović, Ivana, Lavrnja, Irena, Šošić-Jurjević, Branka , Ninković, Milica, Trifunović, Svetlana, "Agmatine reduces chlorpromazine prooxidant effects in rat hippocampus and striatum" in Archives of Biological Sciences, 73, no. 3 (2021):353-359,
https://doi.org/10.2298/abs210429028d . .

TY  - JOUR
AU  - Trifunović, Svetlana
AU  - Stevanović, Ivana
AU  - Milošević, Ana
AU  - Ristić, Nataša
AU  - Janjić, Marija
AU  - Bjelobaba, Ivana
AU  - Savić, Danijela
AU  - Božić, Iva
AU  - Jakovljević, Marija
AU  - Milošević, Katarina
AU  - Laketa, Danijela
AU  - Lavrnja, Irena
PY  - 2021
UR  - https://www.frontiersin.org/articles/10.3389/fnins.2021.649485/full
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4436
AB  - Multiple sclerosis (MS) is an inflammatory, demyelinating disease with an unknown origin. Previous studies showed the involvement of the hypothalamic-pituitary-adrenal (HPA) axis to susceptibility to autoimmune diseases, including MS, and its best-characterized animal model, experimental autoimmune encephalomyelitis (EAE). During MS/EAE, innate immune cells are activated and release cytokines and other inflammatory mediators, leading to a vicious cycle of inflammation. In response to inflammation, the activated HPA axis modulates immune responses via glucocorticoid activity. Because the mechanisms involving oxidative stress to the HPA axis are relatively unrevealed, in this study, we investigate the inflammatory and oxidative stress status of HPA axis during EAE. Our results reveal an upregulation of Pomc gene expression, followed by POMC and ACTH protein increase at the peak of the EAE in the pituitary. Also, prostaglandins are well-known contributors of HPA axis activation, which increases during EAE at the periphery. The upregulated Tnf expression in the pituitary during the peak of EAE occurred. This leads to the activation of oxidative pathways, followed by upregulation of inducible NO synthase expression. The reactive oxidant/nitrosative species (ROS/RNS), such as superoxide anion and NO, increase their levels at the onset and peak of the disease in the pituitary and adrenal glands, returning to control levels at the end of EAE. The corticotrophs in the pituitary increased in number and volume at the peak of EAE that coincides with high lipid peroxidation levels. The expression of MC2R in the adrenal glands increases at the peak of EAE, where strong induction of superoxide anion and malondialdehyde (MDA), reduced total glutathione (GSH) content, and catalase activity occurred at the peak and end of EAE compared with controls. The results obtained from this study may help in understanding the mechanisms and possible pharmacological modulation in MS and demonstrate an effect of oxidative stress exposure in the HPA activation during the course of EAE.
PB  - Lausanne: Frontiers Media SA
T2  - Frontiers in Neuroscience
T1  - The Function of the Hypothalamic-Pituitary-Adrenal Axis During Experimental Autoimmune Encephalomyelitis: Involvement of Oxidative Stress Mediators.
VL  - 15
DO  - 10.3389/fnins.2021.649485
SP  - 649485
ER  - 

@article{
author = "Trifunović, Svetlana and Stevanović, Ivana and Milošević, Ana and Ristić, Nataša and Janjić, Marija and Bjelobaba, Ivana and Savić, Danijela and Božić, Iva and Jakovljević, Marija and Milošević, Katarina and Laketa, Danijela and Lavrnja, Irena",
year = "2021",
abstract = "Multiple sclerosis (MS) is an inflammatory, demyelinating disease with an unknown origin. Previous studies showed the involvement of the hypothalamic-pituitary-adrenal (HPA) axis to susceptibility to autoimmune diseases, including MS, and its best-characterized animal model, experimental autoimmune encephalomyelitis (EAE). During MS/EAE, innate immune cells are activated and release cytokines and other inflammatory mediators, leading to a vicious cycle of inflammation. In response to inflammation, the activated HPA axis modulates immune responses via glucocorticoid activity. Because the mechanisms involving oxidative stress to the HPA axis are relatively unrevealed, in this study, we investigate the inflammatory and oxidative stress status of HPA axis during EAE. Our results reveal an upregulation of Pomc gene expression, followed by POMC and ACTH protein increase at the peak of the EAE in the pituitary. Also, prostaglandins are well-known contributors of HPA axis activation, which increases during EAE at the periphery. The upregulated Tnf expression in the pituitary during the peak of EAE occurred. This leads to the activation of oxidative pathways, followed by upregulation of inducible NO synthase expression. The reactive oxidant/nitrosative species (ROS/RNS), such as superoxide anion and NO, increase their levels at the onset and peak of the disease in the pituitary and adrenal glands, returning to control levels at the end of EAE. The corticotrophs in the pituitary increased in number and volume at the peak of EAE that coincides with high lipid peroxidation levels. The expression of MC2R in the adrenal glands increases at the peak of EAE, where strong induction of superoxide anion and malondialdehyde (MDA), reduced total glutathione (GSH) content, and catalase activity occurred at the peak and end of EAE compared with controls. The results obtained from this study may help in understanding the mechanisms and possible pharmacological modulation in MS and demonstrate an effect of oxidative stress exposure in the HPA activation during the course of EAE.",
publisher = "Lausanne: Frontiers Media SA",
journal = "Frontiers in Neuroscience",
title = "The Function of the Hypothalamic-Pituitary-Adrenal Axis During Experimental Autoimmune Encephalomyelitis: Involvement of Oxidative Stress Mediators.",
volume = "15",
doi = "10.3389/fnins.2021.649485",
pages = "649485"
}

Trifunović, S., Stevanović, I., Milošević, A., Ristić, N., Janjić, M., Bjelobaba, I., Savić, D., Božić, I., Jakovljević, M., Milošević, K., Laketa, D.,& Lavrnja, I.. (2021). The Function of the Hypothalamic-Pituitary-Adrenal Axis During Experimental Autoimmune Encephalomyelitis: Involvement of Oxidative Stress Mediators.. in Frontiers in Neuroscience
Lausanne: Frontiers Media SA., 15, 649485.
https://doi.org/10.3389/fnins.2021.649485

Trifunović S, Stevanović I, Milošević A, Ristić N, Janjić M, Bjelobaba I, Savić D, Božić I, Jakovljević M, Milošević K, Laketa D, Lavrnja I. The Function of the Hypothalamic-Pituitary-Adrenal Axis During Experimental Autoimmune Encephalomyelitis: Involvement of Oxidative Stress Mediators.. in Frontiers in Neuroscience. 2021;15:649485.
doi:10.3389/fnins.2021.649485 .

Trifunović, Svetlana, Stevanović, Ivana, Milošević, Ana, Ristić, Nataša, Janjić, Marija, Bjelobaba, Ivana, Savić, Danijela, Božić, Iva, Jakovljević, Marija, Milošević, Katarina, Laketa, Danijela, Lavrnja, Irena, "The Function of the Hypothalamic-Pituitary-Adrenal Axis During Experimental Autoimmune Encephalomyelitis: Involvement of Oxidative Stress Mediators." in Frontiers in Neuroscience, 15 (2021):649485,
https://doi.org/10.3389/fnins.2021.649485 . .

TY  - JOUR
AU  - Milošević, Ana
AU  - Bjelobaba, Ivana
AU  - Božić, Iva
AU  - Lavrnja, Irena
AU  - Savić, Danijela
AU  - Milošević, Katarina
AU  - Jakovljević, Marija
AU  - Stojilković, Stanko S.
AU  - Janjić, Marija
PY  - 2021
UR  - https://doi.org/10.1038/s41598-021-88305-5
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4248
AB  - Multiple sclerosis (MS) is an autoimmune disease that usually occurs during the reproductive years in both sexes. Many male patients with MS show lower blood testosterone levels, which was also observed in male rats during experimental autoimmune encephalomyelitis (EAE), an animal model of MS. To better understand the causes of decreased testosterone production during EAE, we investigated the expression status of genes and proteins associated with steroidogenesis in the testes. No changes in the number of interstitial cells were observed in EAE animals, but the expression of the insulin-like 3 gene was reduced at the peak of the disease, implying that the Leydig cell functional capacity was affected. Consistent with this finding, the expression of most steroidogenic enzyme genes and proteins was reduced during EAE, including StAR, CYP11A1, CYP17A1 and HSD3B. No signs of testicular inflammation were observed. Recovery of steroidogenesis was observed after injection of hCG, the placental gonadotropin, or buserelin acetate, a gonadotropin-releasing hormone analogue, at the peak of EAE. Together, our results are consistent with the hypothesis that impaired testicular steroidogenesis originates upstream of the testes and that low serum LH is the main cause of decreased testosterone levels during EAE.
PB  - Springer Science and Business Media LLC
T2  - Scientific Reports
T1  - Testicular steroidogenesis is suppressed during experimental autoimmune encephalomyelitis in rats
IS  - 1
VL  - 11
DO  - 10.1038/s41598-021-88305-5
SP  - 8996
ER  - 

@article{
author = "Milošević, Ana and Bjelobaba, Ivana and Božić, Iva and Lavrnja, Irena and Savić, Danijela and Milošević, Katarina and Jakovljević, Marija and Stojilković, Stanko S. and Janjić, Marija",
year = "2021",
abstract = "Multiple sclerosis (MS) is an autoimmune disease that usually occurs during the reproductive years in both sexes. Many male patients with MS show lower blood testosterone levels, which was also observed in male rats during experimental autoimmune encephalomyelitis (EAE), an animal model of MS. To better understand the causes of decreased testosterone production during EAE, we investigated the expression status of genes and proteins associated with steroidogenesis in the testes. No changes in the number of interstitial cells were observed in EAE animals, but the expression of the insulin-like 3 gene was reduced at the peak of the disease, implying that the Leydig cell functional capacity was affected. Consistent with this finding, the expression of most steroidogenic enzyme genes and proteins was reduced during EAE, including StAR, CYP11A1, CYP17A1 and HSD3B. No signs of testicular inflammation were observed. Recovery of steroidogenesis was observed after injection of hCG, the placental gonadotropin, or buserelin acetate, a gonadotropin-releasing hormone analogue, at the peak of EAE. Together, our results are consistent with the hypothesis that impaired testicular steroidogenesis originates upstream of the testes and that low serum LH is the main cause of decreased testosterone levels during EAE.",
publisher = "Springer Science and Business Media LLC",
journal = "Scientific Reports",
title = "Testicular steroidogenesis is suppressed during experimental autoimmune encephalomyelitis in rats",
number = "1",
volume = "11",
doi = "10.1038/s41598-021-88305-5",
pages = "8996"
}

Milošević, A., Bjelobaba, I., Božić, I., Lavrnja, I., Savić, D., Milošević, K., Jakovljević, M., Stojilković, S. S.,& Janjić, M.. (2021). Testicular steroidogenesis is suppressed during experimental autoimmune encephalomyelitis in rats. in Scientific Reports
Springer Science and Business Media LLC., 11(1), 8996.
https://doi.org/10.1038/s41598-021-88305-5

Milošević A, Bjelobaba I, Božić I, Lavrnja I, Savić D, Milošević K, Jakovljević M, Stojilković SS, Janjić M. Testicular steroidogenesis is suppressed during experimental autoimmune encephalomyelitis in rats. in Scientific Reports. 2021;11(1):8996.
doi:10.1038/s41598-021-88305-5 .

Milošević, Ana, Bjelobaba, Ivana, Božić, Iva, Lavrnja, Irena, Savić, Danijela, Milošević, Katarina, Jakovljević, Marija, Stojilković, Stanko S., Janjić, Marija, "Testicular steroidogenesis is suppressed during experimental autoimmune encephalomyelitis in rats" in Scientific Reports, 11, no. 1 (2021):8996,
https://doi.org/10.1038/s41598-021-88305-5 . .

TY  - JOUR
AU  - Božić, Iva
AU  - Savić, Danijela
AU  - Lavrnja, Irena
PY  - 2021
UR  - http://www.ncbi.nlm.nih.gov/pubmed/33226087
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4404
AB  - Astrocytes, the most abundant glial cells in the central nervous system (CNS), have numerous integral roles in all CNS functions. They are essential for synaptic transmission and support neurons by providing metabolic substrates, secreting growth factors and regulating extracellular concentrations of ions and neurotransmitters. Astrocytes respond to CNS insults through reactive astrogliosis, in which they go through many functional and molecular changes. In neuroinflammatory conditions reactive astrocytes exert both beneficial and detrimental functions, depending on the context and heterogeneity of astrocytic populations. In this review we profile astrocytic diversity in the context of neuroinflammation; with a specific focus on multiple sclerosis (MS) and its best-described animal model experimental autoimmune encephalomyelitis (EAE). We characterize two main subtypes, protoplasmic and fibrous astrocytes and describe the role of intermediate filaments in the physiology and pathology of these cells. Additionally, we outline a variety of markers that are emerging as important in investigating astrocytic biology in both physiological conditions and neuroinflammation.
T2  - Histology and Histopathology
T1  - Astrocyte phenotypes: Emphasis on potential markers in neuroinflammation
IS  - 3
VL  - 36
DO  - 10.14670/HH-18-284
SP  - 267
EP  - 290
ER  - 

@article{
author = "Božić, Iva and Savić, Danijela and Lavrnja, Irena",
year = "2021",
abstract = "Astrocytes, the most abundant glial cells in the central nervous system (CNS), have numerous integral roles in all CNS functions. They are essential for synaptic transmission and support neurons by providing metabolic substrates, secreting growth factors and regulating extracellular concentrations of ions and neurotransmitters. Astrocytes respond to CNS insults through reactive astrogliosis, in which they go through many functional and molecular changes. In neuroinflammatory conditions reactive astrocytes exert both beneficial and detrimental functions, depending on the context and heterogeneity of astrocytic populations. In this review we profile astrocytic diversity in the context of neuroinflammation; with a specific focus on multiple sclerosis (MS) and its best-described animal model experimental autoimmune encephalomyelitis (EAE). We characterize two main subtypes, protoplasmic and fibrous astrocytes and describe the role of intermediate filaments in the physiology and pathology of these cells. Additionally, we outline a variety of markers that are emerging as important in investigating astrocytic biology in both physiological conditions and neuroinflammation.",
journal = "Histology and Histopathology",
title = "Astrocyte phenotypes: Emphasis on potential markers in neuroinflammation",
number = "3",
volume = "36",
doi = "10.14670/HH-18-284",
pages = "267-290"
}

Božić, I., Savić, D.,& Lavrnja, I.. (2021). Astrocyte phenotypes: Emphasis on potential markers in neuroinflammation. in Histology and Histopathology, 36(3), 267-290.
https://doi.org/10.14670/HH-18-284

Božić I, Savić D, Lavrnja I. Astrocyte phenotypes: Emphasis on potential markers in neuroinflammation. in Histology and Histopathology. 2021;36(3):267-290.
doi:10.14670/HH-18-284 .

Božić, Iva, Savić, Danijela, Lavrnja, Irena, "Astrocyte phenotypes: Emphasis on potential markers in neuroinflammation" in Histology and Histopathology, 36, no. 3 (2021):267-290,
https://doi.org/10.14670/HH-18-284 . .

TY  - JOUR
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Lavrnja, Irena
AU  - Savić, Danijela
AU  - Božić, Iva
AU  - Milošević, Katarina
AU  - Jakovljević, Marija
AU  - Peković, Sanja
AU  - Stojilkovic, Stanko S.
AU  - Bjelobaba, Ivana
PY  - 2020
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32592862
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6149
AB  - Multiple sclerosis develops during reproductive years in a sex-specific manner. Various neuroendocrine changes have been described in this inflammatory, demyelinating, and debilitating disease. We here aimed to determine the extent and sex specificity of alterations in the hypothalamic-pituitary-gonadal axis in the rat model of multiple sclerosis named experimental autoimmune encephalomyelitis. During the disease course, the hypothalamic tissue showed transient upregulation of inflammatory marker genes Gfap, Cd68, Ccl2, and Il1b in both sexes, but accompanied by sex-specific downregulation of Kiss1 (in females only) and Gnrh1 (in males only) expression. In females, the expression of gonadotrope-specific genes Lhb, Cga, and Gnrhr was also inhibited, accompanied by decreased basal but not stimulated serum luteinizing hormone levels and a transient arrest of the estrous cycle. In contrast, Fshb expression and serum progesterone levels were transiently elevated, findings consistent with the maintenance of the corpora lutea, and elevated immunohistochemical labeling of ovarian StAR, a rate limiting protein in steroidogenic pathway. In males, downregulation of Gnrhr expression and basal and stimulated serum luteinizing hormone and testosterone levels were accompanied by inhibited testicular StAR protein expression. We propose that inflammation of hypothalamic tissue downregulates Kiss1 and Gnrh1 expression in females and males, respectively, leading to sex-specific changes downstream the axis.
PB  - Elsevier BV
PB  - Elsevier
T2  - Brain, Behavior, and Immunity
T1  - The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.
VL  - 89
DO  - 10.1016/j.bbi.2020.06.025
SP  - 233
EP  - 244
ER  - 

@article{
author = "Milošević, Ana and Janjić, Marija and Lavrnja, Irena and Savić, Danijela and Božić, Iva and Milošević, Katarina and Jakovljević, Marija and Peković, Sanja and Stojilkovic, Stanko S. and Bjelobaba, Ivana",
year = "2020",
abstract = "Multiple sclerosis develops during reproductive years in a sex-specific manner. Various neuroendocrine changes have been described in this inflammatory, demyelinating, and debilitating disease. We here aimed to determine the extent and sex specificity of alterations in the hypothalamic-pituitary-gonadal axis in the rat model of multiple sclerosis named experimental autoimmune encephalomyelitis. During the disease course, the hypothalamic tissue showed transient upregulation of inflammatory marker genes Gfap, Cd68, Ccl2, and Il1b in both sexes, but accompanied by sex-specific downregulation of Kiss1 (in females only) and Gnrh1 (in males only) expression. In females, the expression of gonadotrope-specific genes Lhb, Cga, and Gnrhr was also inhibited, accompanied by decreased basal but not stimulated serum luteinizing hormone levels and a transient arrest of the estrous cycle. In contrast, Fshb expression and serum progesterone levels were transiently elevated, findings consistent with the maintenance of the corpora lutea, and elevated immunohistochemical labeling of ovarian StAR, a rate limiting protein in steroidogenic pathway. In males, downregulation of Gnrhr expression and basal and stimulated serum luteinizing hormone and testosterone levels were accompanied by inhibited testicular StAR protein expression. We propose that inflammation of hypothalamic tissue downregulates Kiss1 and Gnrh1 expression in females and males, respectively, leading to sex-specific changes downstream the axis.",
publisher = "Elsevier BV, Elsevier",
journal = "Brain, Behavior, and Immunity",
title = "The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.",
volume = "89",
doi = "10.1016/j.bbi.2020.06.025",
pages = "233-244"
}

Milošević, A., Janjić, M., Lavrnja, I., Savić, D., Božić, I., Milošević, K., Jakovljević, M., Peković, S., Stojilkovic, S. S.,& Bjelobaba, I.. (2020). The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.. in Brain, Behavior, and Immunity
Elsevier BV., 89, 233-244.
https://doi.org/10.1016/j.bbi.2020.06.025

Milošević A, Janjić M, Lavrnja I, Savić D, Božić I, Milošević K, Jakovljević M, Peković S, Stojilkovic SS, Bjelobaba I. The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.. in Brain, Behavior, and Immunity. 2020;89:233-244.
doi:10.1016/j.bbi.2020.06.025 .

Milošević, Ana, Janjić, Marija, Lavrnja, Irena, Savić, Danijela, Božić, Iva, Milošević, Katarina, Jakovljević, Marija, Peković, Sanja, Stojilkovic, Stanko S., Bjelobaba, Ivana, "The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis." in Brain, Behavior, and Immunity, 89 (2020):233-244,
https://doi.org/10.1016/j.bbi.2020.06.025 . .

TY  - JOUR
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Lavrnja, Irena
AU  - Savić, Danijela
AU  - Božić, Iva
AU  - Milošević, Katarina
AU  - Jakovljević, Marija
AU  - Peković, Sanja
AU  - Stojilkovic, Stanko S.
AU  - Bjelobaba, Ivana
PY  - 2020
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32592862
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3762
AB  - Multiple sclerosis develops during reproductive years in a sex-specific manner. Various neuroendocrine changes have been described in this inflammatory, demyelinating, and debilitating disease. We here aimed to determine the extent and sex specificity of alterations in the hypothalamic-pituitary-gonadal axis in the rat model of multiple sclerosis named experimental autoimmune encephalomyelitis. During the disease course, the hypothalamic tissue showed transient upregulation of inflammatory marker genes Gfap, Cd68, Ccl2, and Il1b in both sexes, but accompanied by sex-specific downregulation of Kiss1 (in females only) and Gnrh1 (in males only) expression. In females, the expression of gonadotrope-specific genes Lhb, Cga, and Gnrhr was also inhibited, accompanied by decreased basal but not stimulated serum luteinizing hormone levels and a transient arrest of the estrous cycle. In contrast, Fshb expression and serum progesterone levels were transiently elevated, findings consistent with the maintenance of the corpora lutea, and elevated immunohistochemical labeling of ovarian StAR, a rate limiting protein in steroidogenic pathway. In males, downregulation of Gnrhr expression and basal and stimulated serum luteinizing hormone and testosterone levels were accompanied by inhibited testicular StAR protein expression. We propose that inflammation of hypothalamic tissue downregulates Kiss1 and Gnrh1 expression in females and males, respectively, leading to sex-specific changes downstream the axis.
PB  - Elsevier BV
T2  - Brain, Behavior, and Immunity
T1  - The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.
VL  - 89
DO  - 10.1016/j.bbi.2020.06.025
SP  - DOI:10.1016/j.bbi.2020.06.025
EP  - 244
ER  - 

@article{
author = "Milošević, Ana and Janjić, Marija and Lavrnja, Irena and Savić, Danijela and Božić, Iva and Milošević, Katarina and Jakovljević, Marija and Peković, Sanja and Stojilkovic, Stanko S. and Bjelobaba, Ivana",
year = "2020",
abstract = "Multiple sclerosis develops during reproductive years in a sex-specific manner. Various neuroendocrine changes have been described in this inflammatory, demyelinating, and debilitating disease. We here aimed to determine the extent and sex specificity of alterations in the hypothalamic-pituitary-gonadal axis in the rat model of multiple sclerosis named experimental autoimmune encephalomyelitis. During the disease course, the hypothalamic tissue showed transient upregulation of inflammatory marker genes Gfap, Cd68, Ccl2, and Il1b in both sexes, but accompanied by sex-specific downregulation of Kiss1 (in females only) and Gnrh1 (in males only) expression. In females, the expression of gonadotrope-specific genes Lhb, Cga, and Gnrhr was also inhibited, accompanied by decreased basal but not stimulated serum luteinizing hormone levels and a transient arrest of the estrous cycle. In contrast, Fshb expression and serum progesterone levels were transiently elevated, findings consistent with the maintenance of the corpora lutea, and elevated immunohistochemical labeling of ovarian StAR, a rate limiting protein in steroidogenic pathway. In males, downregulation of Gnrhr expression and basal and stimulated serum luteinizing hormone and testosterone levels were accompanied by inhibited testicular StAR protein expression. We propose that inflammation of hypothalamic tissue downregulates Kiss1 and Gnrh1 expression in females and males, respectively, leading to sex-specific changes downstream the axis.",
publisher = "Elsevier BV",
journal = "Brain, Behavior, and Immunity",
title = "The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.",
volume = "89",
doi = "10.1016/j.bbi.2020.06.025",
pages = "DOI:10.1016/j.bbi.2020.06.025-244"
}

Milošević, A., Janjić, M., Lavrnja, I., Savić, D., Božić, I., Milošević, K., Jakovljević, M., Peković, S., Stojilkovic, S. S.,& Bjelobaba, I.. (2020). The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.. in Brain, Behavior, and Immunity
Elsevier BV., 89, DOI:10.1016/j.bbi.2020.06.025-244.
https://doi.org/10.1016/j.bbi.2020.06.025

Milošević A, Janjić M, Lavrnja I, Savić D, Božić I, Milošević K, Jakovljević M, Peković S, Stojilkovic SS, Bjelobaba I. The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.. in Brain, Behavior, and Immunity. 2020;89:DOI:10.1016/j.bbi.2020.06.025-244.
doi:10.1016/j.bbi.2020.06.025 .

Milošević, Ana, Janjić, Marija, Lavrnja, Irena, Savić, Danijela, Božić, Iva, Milošević, Katarina, Jakovljević, Marija, Peković, Sanja, Stojilkovic, Stanko S., Bjelobaba, Ivana, "The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis." in Brain, Behavior, and Immunity, 89 (2020):DOI:10.1016/j.bbi.2020.06.025-244,
https://doi.org/10.1016/j.bbi.2020.06.025 . .