TY  - JOUR
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Lazarević, Milica
AU  - Ignjatović, Đurđica
AU  - Tomić, Mirko
AU  - Nikolovski, Neda
AU  - Bjelobaba, Ivana
AU  - Momčilović, Miljana
AU  - Dimitrijević, Mirjana
AU  - Miljković, Đorđe
AU  - Stanisavljević, Suzana
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6643
AB  - We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund’s adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.
PB  - Elsevier
T2  - Immunology Letters
T1  - Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate
VL  - 267
DO  - 10.1016/j.imlet.2024.106852
SP  - 106852
ER  - 

@article{
author = "Stegnjaić, Goran and Jevtić, Bojan and Lazarević, Milica and Ignjatović, Đurđica and Tomić, Mirko and Nikolovski, Neda and Bjelobaba, Ivana and Momčilović, Miljana and Dimitrijević, Mirjana and Miljković, Đorđe and Stanisavljević, Suzana",
year = "2024",
abstract = "We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund’s adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.",
publisher = "Elsevier",
journal = "Immunology Letters",
title = "Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate",
volume = "267",
doi = "10.1016/j.imlet.2024.106852",
pages = "106852"
}

Stegnjaić, G., Jevtić, B., Lazarević, M., Ignjatović, Đ., Tomić, M., Nikolovski, N., Bjelobaba, I., Momčilović, M., Dimitrijević, M., Miljković, Đ.,& Stanisavljević, S.. (2024). Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate. in Immunology Letters
Elsevier., 267, 106852.
https://doi.org/10.1016/j.imlet.2024.106852

Stegnjaić G, Jevtić B, Lazarević M, Ignjatović Đ, Tomić M, Nikolovski N, Bjelobaba I, Momčilović M, Dimitrijević M, Miljković Đ, Stanisavljević S. Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate. in Immunology Letters. 2024;267:106852.
doi:10.1016/j.imlet.2024.106852 .

Stegnjaić, Goran, Jevtić, Bojan, Lazarević, Milica, Ignjatović, Đurđica, Tomić, Mirko, Nikolovski, Neda, Bjelobaba, Ivana, Momčilović, Miljana, Dimitrijević, Mirjana, Miljković, Đorđe, Stanisavljević, Suzana, "Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate" in Immunology Letters, 267 (2024):106852,
https://doi.org/10.1016/j.imlet.2024.106852 . .

TY  - JOUR
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Lazarević, Milica
AU  - Ignjatović, Đurđica
AU  - Tomić, Mirko
AU  - Nikolovski, Neda
AU  - Bjelobaba, Ivana
AU  - Momčilović, Miljana
AU  - Dimitrijević, Mirjana
AU  - Miljković, Đorđe
AU  - Stanisavljević, Suzana
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6644
AB  - We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund’s adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.
PB  - Elsevier
T2  - Immunology Letters
T1  - Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate
VL  - 267
DO  - 10.1016/j.imlet.2024.106852
SP  - 106852
ER  - 

@article{
author = "Stegnjaić, Goran and Jevtić, Bojan and Lazarević, Milica and Ignjatović, Đurđica and Tomić, Mirko and Nikolovski, Neda and Bjelobaba, Ivana and Momčilović, Miljana and Dimitrijević, Mirjana and Miljković, Đorđe and Stanisavljević, Suzana",
year = "2024",
abstract = "We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund’s adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.",
publisher = "Elsevier",
journal = "Immunology Letters",
title = "Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate",
volume = "267",
doi = "10.1016/j.imlet.2024.106852",
pages = "106852"
}

Stegnjaić, G., Jevtić, B., Lazarević, M., Ignjatović, Đ., Tomić, M., Nikolovski, N., Bjelobaba, I., Momčilović, M., Dimitrijević, M., Miljković, Đ.,& Stanisavljević, S.. (2024). Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate. in Immunology Letters
Elsevier., 267, 106852.
https://doi.org/10.1016/j.imlet.2024.106852

Stegnjaić G, Jevtić B, Lazarević M, Ignjatović Đ, Tomić M, Nikolovski N, Bjelobaba I, Momčilović M, Dimitrijević M, Miljković Đ, Stanisavljević S. Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate. in Immunology Letters. 2024;267:106852.
doi:10.1016/j.imlet.2024.106852 .

Stegnjaić, Goran, Jevtić, Bojan, Lazarević, Milica, Ignjatović, Đurđica, Tomić, Mirko, Nikolovski, Neda, Bjelobaba, Ivana, Momčilović, Miljana, Dimitrijević, Mirjana, Miljković, Đorđe, Stanisavljević, Suzana, "Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate" in Immunology Letters, 267 (2024):106852,
https://doi.org/10.1016/j.imlet.2024.106852 . .

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  - 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  - 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  - Sokanović, Srđan
AU  - Constantin, Stephanie
AU  - Lamarca Dams, Aloa
AU  - Mochimaru, Yuta
AU  - Smiljanić, Kosara
AU  - Bjelobaba, Ivana
AU  - Prévide, Rafael
AU  - Stojilković, Stanko
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5854
AB  - Simultaneous knockout of the neuroendocrine marker genes Ptprn and Ptprn2, which 
encode the protein tyrosine phosphatase receptors N and N2, respectively, causes 
infertility of female mice while males are fertile. To clarify the mechanism of sex specific roles of Ptprn and Ptprn2 in mice reproduction, we analyzed the effects of 
their double knockout (DKO) on the hypothalamic-pituitary-gonadal axis. In DKO 
females, a delay in puberty and lack of ovulation were observed, supplemented by 
changes in ovarian gene expression and steroidogenesis. In DKO males, the testicular 
gene expression, steroidogenesis, and development of reproductive organs were not 
affected. However, in both sexes, pituitary luteinizing hormone (LH) beta gene
expression and LH levels were reduced, while the calcium-mobilizing and LH 
secretory actions of gonadotropin-releasing hormone (GnRH) receptors were 
preserved. The expression of hypothalamic Gnrh1 and Kiss1 genes were also reduced 
in DKO females and males. The density of immunoreactive GnRH fibers was 
decreased in the median eminence in DKO females and males. The density of 
immunoreactive kisspeptin fibers was also decreased in the rostral periventricular 
region of the third ventricle of females and in the arcuate nucleus of females and 
males. Therefore, infertility in DKO females cannot be explained only by sex-specific 
gonadotroph impairment. Instead, changes in hypothalamic gene expression, 
specifically Kiss1 in the rostral periventricular region of the third ventricle, might 
provide an alternative hypothesis due to its sexual dimorphism and involvement in 
puberty onset and ovulation.
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  - Protein tyrosine phosphatase receptors N and N2 regulate  gonadotropin-releasing hormone neuron function
SP  - 107
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5854
ER  - 

@conference{
author = "Sokanović, Srđan and Constantin, Stephanie and Lamarca Dams, Aloa and Mochimaru, Yuta and Smiljanić, Kosara and Bjelobaba, Ivana and Prévide, Rafael and Stojilković, Stanko",
year = "2023",
abstract = "Simultaneous knockout of the neuroendocrine marker genes Ptprn and Ptprn2, which 
encode the protein tyrosine phosphatase receptors N and N2, respectively, causes 
infertility of female mice while males are fertile. To clarify the mechanism of sex specific roles of Ptprn and Ptprn2 in mice reproduction, we analyzed the effects of 
their double knockout (DKO) on the hypothalamic-pituitary-gonadal axis. In DKO 
females, a delay in puberty and lack of ovulation were observed, supplemented by 
changes in ovarian gene expression and steroidogenesis. In DKO males, the testicular 
gene expression, steroidogenesis, and development of reproductive organs were not 
affected. However, in both sexes, pituitary luteinizing hormone (LH) beta gene
expression and LH levels were reduced, while the calcium-mobilizing and LH 
secretory actions of gonadotropin-releasing hormone (GnRH) receptors were 
preserved. The expression of hypothalamic Gnrh1 and Kiss1 genes were also reduced 
in DKO females and males. The density of immunoreactive GnRH fibers was 
decreased in the median eminence in DKO females and males. The density of 
immunoreactive kisspeptin fibers was also decreased in the rostral periventricular 
region of the third ventricle of females and in the arcuate nucleus of females and 
males. Therefore, infertility in DKO females cannot be explained only by sex-specific 
gonadotroph impairment. Instead, changes in hypothalamic gene expression, 
specifically Kiss1 in the rostral periventricular region of the third ventricle, might 
provide an alternative hypothesis due to its sexual dimorphism and involvement in 
puberty onset and ovulation.",
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 = "Protein tyrosine phosphatase receptors N and N2 regulate  gonadotropin-releasing hormone neuron function",
pages = "107",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5854"
}

Sokanović, S., Constantin, S., Lamarca Dams, A., Mochimaru, Y., Smiljanić, K., Bjelobaba, I., Prévide, R.,& Stojilković, S.. (2023). Protein tyrosine phosphatase receptors N and N2 regulate  gonadotropin-releasing hormone neuron function. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 107.
https://hdl.handle.net/21.15107/rcub_ibiss_5854

Sokanović S, Constantin S, Lamarca Dams A, Mochimaru Y, Smiljanić K, Bjelobaba I, Prévide R, Stojilković S. Protein tyrosine phosphatase receptors N and N2 regulate  gonadotropin-releasing hormone neuron function. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:107.
https://hdl.handle.net/21.15107/rcub_ibiss_5854 .

Sokanović, Srđan, Constantin, Stephanie, Lamarca Dams, Aloa, Mochimaru, Yuta, Smiljanić, Kosara, Bjelobaba, Ivana, Prévide, Rafael, Stojilković, Stanko, "Protein tyrosine phosphatase receptors N and N2 regulate  gonadotropin-releasing hormone neuron function" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):107,
https://hdl.handle.net/21.15107/rcub_ibiss_5854 .

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  - Sokanović, Srđan
AU  - Constantin, Stephanie
AU  - Dams, Aloa Lamarca
AU  - Mochimaru, Yuta
AU  - Smiljanić, Kosara
AU  - Bjelobaba, Ivana
AU  - Prévide, Rafael
AU  - Stojilković, Stanko
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5382
AB  - Simultaneous knockout of the neuroendocrine marker genes Ptprn and Ptprn2, which encode the protein tyrosine phosphatase receptors N and N2, causes infertility in female mice while males are fertile. To elucidate the mechanism of the sex-specific roles of Ptprn and Ptprn2 in mouse reproduction, we analyzed the effects of their double knockout (DKO) on the hypothalamic-pituitary-gonadal axis. In DKO females, delayed puberty and lack of ovulation were observed, complemented by changes in ovarian gene expression and steroidogenesis. In contrast, testicular gene expression, steroidogenesis, and reproductive organs development were not significantly affected in DKO males. However, in both sexes, pituitary luteinizing hormone (LH) beta gene expression and LH levels were reduced, as well as follicle-stimulating hormone beta gene and gonadotropin-releasing hormone (GnRH) gene, while the calcium-mobilizing and LH secretory actions of GnRH were preserved. Hypothalamic Gnrh1 and Kiss1 gene expression was also reduced in DKO females and males. In parallel, a significant decrease in the density of immunoreactive GnRH and kisspeptin fibers was detected in the hypothalamic arcuate nucleus of DKO females and males. The female-specific kisspeptin immunoreactivity in the rostral periventricular region of the third ventricle was also reduced in DKO females, but not in DKO males. These data indicate a critical role of Ptprn and Ptprn2 in kisspeptin-GnRH neuronal function and sexual dimorphism in the threshold levels of GnRH required to preserve reproductive functions.
PB  - Springer Nature
T2  - Scientific Reports
T1  - Common and female-specific roles of proteine tyrosine phosphatase receptors N and N2 in mice reproduction
VL  - 13
DO  - 10.1038/s41598-023-27497-4
SP  - 1
SP  - 355
ER  - 

@article{
author = "Sokanović, Srđan and Constantin, Stephanie and Dams, Aloa Lamarca and Mochimaru, Yuta and Smiljanić, Kosara and Bjelobaba, Ivana and Prévide, Rafael and Stojilković, Stanko",
year = "2023",
abstract = "Simultaneous knockout of the neuroendocrine marker genes Ptprn and Ptprn2, which encode the protein tyrosine phosphatase receptors N and N2, causes infertility in female mice while males are fertile. To elucidate the mechanism of the sex-specific roles of Ptprn and Ptprn2 in mouse reproduction, we analyzed the effects of their double knockout (DKO) on the hypothalamic-pituitary-gonadal axis. In DKO females, delayed puberty and lack of ovulation were observed, complemented by changes in ovarian gene expression and steroidogenesis. In contrast, testicular gene expression, steroidogenesis, and reproductive organs development were not significantly affected in DKO males. However, in both sexes, pituitary luteinizing hormone (LH) beta gene expression and LH levels were reduced, as well as follicle-stimulating hormone beta gene and gonadotropin-releasing hormone (GnRH) gene, while the calcium-mobilizing and LH secretory actions of GnRH were preserved. Hypothalamic Gnrh1 and Kiss1 gene expression was also reduced in DKO females and males. In parallel, a significant decrease in the density of immunoreactive GnRH and kisspeptin fibers was detected in the hypothalamic arcuate nucleus of DKO females and males. The female-specific kisspeptin immunoreactivity in the rostral periventricular region of the third ventricle was also reduced in DKO females, but not in DKO males. These data indicate a critical role of Ptprn and Ptprn2 in kisspeptin-GnRH neuronal function and sexual dimorphism in the threshold levels of GnRH required to preserve reproductive functions.",
publisher = "Springer Nature",
journal = "Scientific Reports",
title = "Common and female-specific roles of proteine tyrosine phosphatase receptors N and N2 in mice reproduction",
volume = "13",
doi = "10.1038/s41598-023-27497-4",
pages = "1-355"
}

Sokanović, S., Constantin, S., Dams, A. L., Mochimaru, Y., Smiljanić, K., Bjelobaba, I., Prévide, R.,& Stojilković, S.. (2023). Common and female-specific roles of proteine tyrosine phosphatase receptors N and N2 in mice reproduction. in Scientific Reports
Springer Nature., 13, 1.
https://doi.org/10.1038/s41598-023-27497-4

Sokanović S, Constantin S, Dams AL, Mochimaru Y, Smiljanić K, Bjelobaba I, Prévide R, Stojilković S. Common and female-specific roles of proteine tyrosine phosphatase receptors N and N2 in mice reproduction. in Scientific Reports. 2023;13:1.
doi:10.1038/s41598-023-27497-4 .

Sokanović, Srđan, Constantin, Stephanie, Dams, Aloa Lamarca, Mochimaru, Yuta, Smiljanić, Kosara, Bjelobaba, Ivana, Prévide, Rafael, Stojilković, Stanko, "Common and female-specific roles of proteine tyrosine phosphatase receptors N and N2 in mice reproduction" in Scientific Reports, 13 (2023):1,
https://doi.org/10.1038/s41598-023-27497-4 . .

TY  - JOUR
AU  - Constantin, Stephanie
AU  - Bjelobaba, Ivana
AU  - Stojilković, Stanko S.
PY  - 2022
UR  - https://linkinghub.elsevier.com/retrieve/pii/S1471489222001011
UR  - http://www.ncbi.nlm.nih.gov/pubmed/35994915
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9509429
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5105
AB  - Pituitary gonadotrophs play a key role in reproductive functions by secreting luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The LH secretory activity of gonadotroph is controlled by hypothalamic gonadotropin-releasing hormone (GnRH) via GnRH receptors and is accompanied by only minor effects on high basal Lhb gene expression. The secretory profiles of GnRH and LH are highly synchronized, with the latter reflecting a depletion of prestored LH in secretory vesicles by regulated exocytosis. In contrast, FSH is predominantly released by constitutive exocytosis, and secretory activity reflects the kinetics of Fshb gene expression controlled by GnRH, activin, and inhibin. Here is a review of recent data to improve the understanding of multiple patterns of gonadotroph gene expression and hormone secretion.
PB  - Elsevier B.V.
T2  - Current Opinion in Pharmacology
T1  - Pituitary gonadotroph-specific patterns of gene expression and hormone secretion.
VL  - 66
DO  - 10.1016/j.coph.2022.102274
SP  - 102274
ER  - 

@article{
author = "Constantin, Stephanie and Bjelobaba, Ivana and Stojilković, Stanko S.",
year = "2022",
abstract = "Pituitary gonadotrophs play a key role in reproductive functions by secreting luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The LH secretory activity of gonadotroph is controlled by hypothalamic gonadotropin-releasing hormone (GnRH) via GnRH receptors and is accompanied by only minor effects on high basal Lhb gene expression. The secretory profiles of GnRH and LH are highly synchronized, with the latter reflecting a depletion of prestored LH in secretory vesicles by regulated exocytosis. In contrast, FSH is predominantly released by constitutive exocytosis, and secretory activity reflects the kinetics of Fshb gene expression controlled by GnRH, activin, and inhibin. Here is a review of recent data to improve the understanding of multiple patterns of gonadotroph gene expression and hormone secretion.",
publisher = "Elsevier B.V.",
journal = "Current Opinion in Pharmacology",
title = "Pituitary gonadotroph-specific patterns of gene expression and hormone secretion.",
volume = "66",
doi = "10.1016/j.coph.2022.102274",
pages = "102274"
}

Constantin, S., Bjelobaba, I.,& Stojilković, S. S.. (2022). Pituitary gonadotroph-specific patterns of gene expression and hormone secretion.. in Current Opinion in Pharmacology
Elsevier B.V.., 66, 102274.
https://doi.org/10.1016/j.coph.2022.102274

Constantin S, Bjelobaba I, Stojilković SS. Pituitary gonadotroph-specific patterns of gene expression and hormone secretion.. in Current Opinion in Pharmacology. 2022;66:102274.
doi:10.1016/j.coph.2022.102274 .

Constantin, Stephanie, Bjelobaba, Ivana, Stojilković, Stanko S., "Pituitary gonadotroph-specific patterns of gene expression and hormone secretion." in Current Opinion in Pharmacology, 66 (2022):102274,
https://doi.org/10.1016/j.coph.2022.102274 . .

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  - 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  - 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  - 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  - 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 . .

TY  - JOUR
AU  - Bjelobaba, Ivana
AU  - Kanazir, Selma
PY  - 2020
UR  - http://hrana-ishrana.org/wp-content/uploads/2021/03/Broj-2-Vol-61-2020-1.pdf
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4180
AB  - Sve veći broj podataka ukazuje na to da infekcija virusom SARS-CoV-2
može uticati na nervni sistem. Ovde predstavljamo kratak, uzdržan pregled
opisanih neuroloških oštećenja povezanih sa SARS-CoV-2 infekcijom. Iako
je očigledno da se neurološki poremećaji mogu dijagnostikovati kod dela
COVID-19 pacijenata, čvrsti dokazi o neurovirulenciji SARS-CoV-2 još uvek
nedostaju. Postojeći podaci o učestalosti neuroloških poremećaja među
COVID-19 pacijentima veoma su raznoliki, verovatno zato što (najčešće)
potiču iz malih, unicentričnih retrospektivnih studija. Ovi podaci se praktično
objavljuju u realnom vremenu i ostaje pitanje kada će biti dostupne veće
studije, s obzirom na to da se pandemija nastavlja. Ovde se ukratko bavimo
i drugim pitanjima u vezi sa neurološkim poremećajima i pandemijom COVID-
19, uključujući tu i uticaj pandemije na ljude sa postojećim hroničnim
neurološkim poremećajima i moguće dugoročne neurološke posledice infekcije
SARS-CoV-2.
AB  - The growing body of data implies that SARS-CoV-2 infection may affect
the nervous system. We here present a short, taciturn overview of
described neurological impairments related to SARS-CoV-2 infection.
While it is obvious that neurological impairments can be diagnosed in a
portion of COVID-19 patients, evidence of SARS-CoV-2 neurovirulence in
humans is still lacking. The existing data on the incidence of neurological
impairments among COVID-19 patients is highly variable, probably
because they (most often) come from small, single-center retrospective
studies. These data are practically published in real-time, and the
question remains when larger studies will be available, given that the
pandemic is continuing. We here also shortly address the other issues
related to neurological disorders and COVID-19 pandemic, including
the concern for people with existing chronic neurological disorders and
possible long-term neurological consequences of SARS-CoV-2 infection.
PB  - Belgrade: Serbian Nutrition Society
T2  - Hrana i ishrana
T1  - Neurological impairments in COVID-19 pandemic
T1  - Neurološki poremećaji i pandemija Covid -19
IS  - 2
VL  - 61
DO  - 10.5937/hraIsh2002071B
SP  - 71
EP  - 77
ER  - 

@article{
author = "Bjelobaba, Ivana and Kanazir, Selma",
year = "2020",
abstract = "Sve veći broj podataka ukazuje na to da infekcija virusom SARS-CoV-2
može uticati na nervni sistem. Ovde predstavljamo kratak, uzdržan pregled
opisanih neuroloških oštećenja povezanih sa SARS-CoV-2 infekcijom. Iako
je očigledno da se neurološki poremećaji mogu dijagnostikovati kod dela
COVID-19 pacijenata, čvrsti dokazi o neurovirulenciji SARS-CoV-2 još uvek
nedostaju. Postojeći podaci o učestalosti neuroloških poremećaja među
COVID-19 pacijentima veoma su raznoliki, verovatno zato što (najčešće)
potiču iz malih, unicentričnih retrospektivnih studija. Ovi podaci se praktično
objavljuju u realnom vremenu i ostaje pitanje kada će biti dostupne veće
studije, s obzirom na to da se pandemija nastavlja. Ovde se ukratko bavimo
i drugim pitanjima u vezi sa neurološkim poremećajima i pandemijom COVID-
19, uključujući tu i uticaj pandemije na ljude sa postojećim hroničnim
neurološkim poremećajima i moguće dugoročne neurološke posledice infekcije
SARS-CoV-2., The growing body of data implies that SARS-CoV-2 infection may affect
the nervous system. We here present a short, taciturn overview of
described neurological impairments related to SARS-CoV-2 infection.
While it is obvious that neurological impairments can be diagnosed in a
portion of COVID-19 patients, evidence of SARS-CoV-2 neurovirulence in
humans is still lacking. The existing data on the incidence of neurological
impairments among COVID-19 patients is highly variable, probably
because they (most often) come from small, single-center retrospective
studies. These data are practically published in real-time, and the
question remains when larger studies will be available, given that the
pandemic is continuing. We here also shortly address the other issues
related to neurological disorders and COVID-19 pandemic, including
the concern for people with existing chronic neurological disorders and
possible long-term neurological consequences of SARS-CoV-2 infection.",
publisher = "Belgrade: Serbian Nutrition Society",
journal = "Hrana i ishrana",
title = "Neurological impairments in COVID-19 pandemic, Neurološki poremećaji i pandemija Covid -19",
number = "2",
volume = "61",
doi = "10.5937/hraIsh2002071B",
pages = "71-77"
}

Bjelobaba, I.,& Kanazir, S.. (2020). Neurological impairments in COVID-19 pandemic. in Hrana i ishrana
Belgrade: Serbian Nutrition Society., 61(2), 71-77.
https://doi.org/10.5937/hraIsh2002071B

Bjelobaba I, Kanazir S. Neurological impairments in COVID-19 pandemic. in Hrana i ishrana. 2020;61(2):71-77.
doi:10.5937/hraIsh2002071B .

Bjelobaba, Ivana, Kanazir, Selma, "Neurological impairments in COVID-19 pandemic" in Hrana i ishrana, 61, no. 2 (2020):71-77,
https://doi.org/10.5937/hraIsh2002071B . .

TY  - CONF
AU  - Janjić, Marija
AU  - Milošević, Ana
AU  - Bjelobaba, Ivana
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5973
AB  - Two gonadotropins, luteinizing hormone and follicle-stimulating hormone, are synthetized and secreted by anterior pituitary gonadotropes and act on the gonads, controlling gametogenesis and sex hormone production. These hormones are glycoprotein polypeptides, composed of specific beta subunits and a common, alpha subunit. Both transcription and secretion of gonadotropins are regulated by gonadotropin-releasing hormone (GnRH), which is produced by small number of hypothalamic neurons within the preoptic area and mediobasal hypothalamus. GnRH is released and is reaching the pituitary in pulses, a pattern of secretion that is crucial for the proper reproductive functions. This mini review covers mechanisms of transcriptional control of gonadotropin subunit genes by GnRH, predominantly focusing on in vivo experiments with mice and rats and in vitro experiments using primary pituitary cell cultures and immortalized pituitary cell lines derived from these species. We also provide an overview of the promoter regions of gonadotropin genes and major transcription factors involved in GnRH-driven expression of gonadotropin subunit genes.
PB  - Belgrade: Faculty of Chemistry
C3  - The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia
T1  - Gonadotropin-releasing hormone regulated transcription of gonadotropin subunit genes
SP  - 47
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5973
ER  - 

@conference{
author = "Janjić, Marija and Milošević, Ana and Bjelobaba, Ivana",
year = "2019",
abstract = "Two gonadotropins, luteinizing hormone and follicle-stimulating hormone, are synthetized and secreted by anterior pituitary gonadotropes and act on the gonads, controlling gametogenesis and sex hormone production. These hormones are glycoprotein polypeptides, composed of specific beta subunits and a common, alpha subunit. Both transcription and secretion of gonadotropins are regulated by gonadotropin-releasing hormone (GnRH), which is produced by small number of hypothalamic neurons within the preoptic area and mediobasal hypothalamus. GnRH is released and is reaching the pituitary in pulses, a pattern of secretion that is crucial for the proper reproductive functions. This mini review covers mechanisms of transcriptional control of gonadotropin subunit genes by GnRH, predominantly focusing on in vivo experiments with mice and rats and in vitro experiments using primary pituitary cell cultures and immortalized pituitary cell lines derived from these species. We also provide an overview of the promoter regions of gonadotropin genes and major transcription factors involved in GnRH-driven expression of gonadotropin subunit genes.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia",
title = "Gonadotropin-releasing hormone regulated transcription of gonadotropin subunit genes",
pages = "47",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5973"
}

Janjić, M., Milošević, A.,& Bjelobaba, I.. (2019). Gonadotropin-releasing hormone regulated transcription of gonadotropin subunit genes. in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia
Belgrade: Faculty of Chemistry., 47.
https://hdl.handle.net/21.15107/rcub_ibiss_5973

Janjić M, Milošević A, Bjelobaba I. Gonadotropin-releasing hormone regulated transcription of gonadotropin subunit genes. in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia. 2019;:47.
https://hdl.handle.net/21.15107/rcub_ibiss_5973 .

Janjić, Marija, Milošević, Ana, Bjelobaba, Ivana, "Gonadotropin-releasing hormone regulated transcription of gonadotropin subunit genes" in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia (2019):47,
https://hdl.handle.net/21.15107/rcub_ibiss_5973 .

TY  - JOUR
AU  - Božić, Iva
AU  - Savić, Danijela
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Laketa, Danijela
AU  - Milošević, Katarina
AU  - Bjelobaba, Ivana
AU  - Jakovljević, Marija
AU  - Nedeljković, Nadežda
AU  - Peković, Sanja
AU  - Lavrnja, Irena
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5874
AB  - Multiple sclerosis (MS) is a chronic, inflammatory, neurodegenerative disease with an autoimmune component. It was suggested that potassium channels, which are involved in crucial biological functions may have a role in different diseases, including MS and its animal model, experimental autoimmune encephalomyelitis (EAE). It was shown that voltage-gated potassium channels Kv1.5 are responsible for fine-tuning in the immune physiology and influence proliferation and differentiation in microglia and astrocytes. Here, we explored the cellular distribution of the Kv1.5 channel, together with its transcript and protein expression in the male rat spinal cord during different stages of EAE. Our results reveal a decrease of Kv1.5 transcript and protein level at the peak of disease, where massive infiltration of myeloid cells occurs, together with reactive astrogliosis and demyelination. Also, we revealed that the presence of this channel is not found in infiltrating macrophages/microglia during EAE. It is interesting to note that Kv1.5 channel is expressed only in resting microglia in the naïve animals. Predominant expression of Kv1.5 channel was found in the astrocytes in all experimental groups, while some vimentin+ cells, resembling macrophages, are devoid of Kv1.5 expression. Our results point to the possible link between Kv1.5 channel and the pathophysiological processes in EAE.
PB  - New York: Springer
T2  - Neurochemical Research
T1  - The Potassium Channel Kv1.5 Expression Alters During Experimental  Autoimmune Encephalomyelitis
IS  - 12
VL  - 44
DO  - 10.1007/s11064-019-02892-4
SP  - 2733
EP  - 2745
ER  - 

@article{
author = "Božić, Iva and Savić, Danijela and Milošević, Ana and Janjić, Marija and Laketa, Danijela and Milošević, Katarina and Bjelobaba, Ivana and Jakovljević, Marija and Nedeljković, Nadežda and Peković, Sanja and Lavrnja, Irena",
year = "2019",
abstract = "Multiple sclerosis (MS) is a chronic, inflammatory, neurodegenerative disease with an autoimmune component. It was suggested that potassium channels, which are involved in crucial biological functions may have a role in different diseases, including MS and its animal model, experimental autoimmune encephalomyelitis (EAE). It was shown that voltage-gated potassium channels Kv1.5 are responsible for fine-tuning in the immune physiology and influence proliferation and differentiation in microglia and astrocytes. Here, we explored the cellular distribution of the Kv1.5 channel, together with its transcript and protein expression in the male rat spinal cord during different stages of EAE. Our results reveal a decrease of Kv1.5 transcript and protein level at the peak of disease, where massive infiltration of myeloid cells occurs, together with reactive astrogliosis and demyelination. Also, we revealed that the presence of this channel is not found in infiltrating macrophages/microglia during EAE. It is interesting to note that Kv1.5 channel is expressed only in resting microglia in the naïve animals. Predominant expression of Kv1.5 channel was found in the astrocytes in all experimental groups, while some vimentin+ cells, resembling macrophages, are devoid of Kv1.5 expression. Our results point to the possible link between Kv1.5 channel and the pathophysiological processes in EAE.",
publisher = "New York: Springer",
journal = "Neurochemical Research",
title = "The Potassium Channel Kv1.5 Expression Alters During Experimental  Autoimmune Encephalomyelitis",
number = "12",
volume = "44",
doi = "10.1007/s11064-019-02892-4",
pages = "2733-2745"
}

Božić, I., Savić, D., Milošević, A., Janjić, M., Laketa, D., Milošević, K., Bjelobaba, I., Jakovljević, M., Nedeljković, N., Peković, S.,& Lavrnja, I.. (2019). The Potassium Channel Kv1.5 Expression Alters During Experimental  Autoimmune Encephalomyelitis. in Neurochemical Research
New York: Springer., 44(12), 2733-2745.
https://doi.org/10.1007/s11064-019-02892-4

Božić I, Savić D, Milošević A, Janjić M, Laketa D, Milošević K, Bjelobaba I, Jakovljević M, Nedeljković N, Peković S, Lavrnja I. The Potassium Channel Kv1.5 Expression Alters During Experimental  Autoimmune Encephalomyelitis. in Neurochemical Research. 2019;44(12):2733-2745.
doi:10.1007/s11064-019-02892-4 .

Božić, Iva, Savić, Danijela, Milošević, Ana, Janjić, Marija, Laketa, Danijela, Milošević, Katarina, Bjelobaba, Ivana, Jakovljević, Marija, Nedeljković, Nadežda, Peković, Sanja, Lavrnja, Irena, "The Potassium Channel Kv1.5 Expression Alters During Experimental  Autoimmune Encephalomyelitis" in Neurochemical Research, 44, no. 12 (2019):2733-2745,
https://doi.org/10.1007/s11064-019-02892-4 . .

TY  - JOUR
AU  - Janjić, Marija
AU  - Milošević, Ana
AU  - Bjelobaba, Ivana
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5974
AB  - Two gonadotropins, luteinizing hormone and follicle-stimulating hormone, are synthetized and secreted by anterior pituitary gonadotropes and act on the gonads, controlling gametogenesis and sex hormone production. These hormones are glycoprotein polypeptides, composed of specific beta subunits and a common, alpha subunit. Both transcription and secretion of gonadotropins are regulated by gonadotropin-releasing hormone (GnRH), which is produced by a small number of hypothalamic neurons within the preoptic area and mediobasal hypothalamus. GnRH is released and reaches the pituitary in pulses, a pattern of secretion that is crucial for proper reproductive functions. This mini review covers mechanisms of transcriptional control of gonadotropin subunit genes by GnRH, predominantly focusing on in vivo experiments with mice and rats and in vitro experiments using primary pituitary cell cultures and immortalized pituitary cell lines derived from these species. We also provide an overview of the promoter regions of gonadotropin genes and major transcription factors involved in GnRH-driven expression of gonadotropin subunit genes.
PB  - Novi Sad: Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad
T2  - Biologia Serbica
T1  - Gonadotropin-releasing hormone regulated transcription of gonadotropin subunit genes
IS  - 2
VL  - 41
DO  - 10.5281/zenodo.3532061
SP  - 51
EP  - 56
ER  - 

@article{
author = "Janjić, Marija and Milošević, Ana and Bjelobaba, Ivana",
year = "2019",
abstract = "Two gonadotropins, luteinizing hormone and follicle-stimulating hormone, are synthetized and secreted by anterior pituitary gonadotropes and act on the gonads, controlling gametogenesis and sex hormone production. These hormones are glycoprotein polypeptides, composed of specific beta subunits and a common, alpha subunit. Both transcription and secretion of gonadotropins are regulated by gonadotropin-releasing hormone (GnRH), which is produced by a small number of hypothalamic neurons within the preoptic area and mediobasal hypothalamus. GnRH is released and reaches the pituitary in pulses, a pattern of secretion that is crucial for proper reproductive functions. This mini review covers mechanisms of transcriptional control of gonadotropin subunit genes by GnRH, predominantly focusing on in vivo experiments with mice and rats and in vitro experiments using primary pituitary cell cultures and immortalized pituitary cell lines derived from these species. We also provide an overview of the promoter regions of gonadotropin genes and major transcription factors involved in GnRH-driven expression of gonadotropin subunit genes.",
publisher = "Novi Sad: Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad",
journal = "Biologia Serbica",
title = "Gonadotropin-releasing hormone regulated transcription of gonadotropin subunit genes",
number = "2",
volume = "41",
doi = "10.5281/zenodo.3532061",
pages = "51-56"
}

Janjić, M., Milošević, A.,& Bjelobaba, I.. (2019). Gonadotropin-releasing hormone regulated transcription of gonadotropin subunit genes. in Biologia Serbica
Novi Sad: Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad., 41(2), 51-56.
https://doi.org/10.5281/zenodo.3532061

Janjić M, Milošević A, Bjelobaba I. Gonadotropin-releasing hormone regulated transcription of gonadotropin subunit genes. in Biologia Serbica. 2019;41(2):51-56.
doi:10.5281/zenodo.3532061 .

Janjić, Marija, Milošević, Ana, Bjelobaba, Ivana, "Gonadotropin-releasing hormone regulated transcription of gonadotropin subunit genes" in Biologia Serbica, 41, no. 2 (2019):51-56,
https://doi.org/10.5281/zenodo.3532061 . .

TY  - CONF
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Lavrnja, Irena
AU  - Peković, Sanja
AU  - Bjelobaba, Ivana
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5979
AB  - Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease, two to three times more common in women than in men. Because the effects of neuroinflammation on the reproductive status have not been fully explored, our aim was to investigate the impact of experimental autoimmune encephalomyelitis (EAE), the rat model of MS, on hypothalamo-pituitary-gonadal axis. EAE was actively induced in Dark-Agouti rats of both sexes. The animals were examined daily for disease symptoms, weight changes, and estrous cycle phase. The animals were sacrificed at the onset, peak, and end of the disease. Hypothalamic and pituitary tissues were dissected for qRT-PCR analyses. Blood was collected for LH measurements. In separate experiments, groups of male and female animals at the peak of EAE and naïve controls received a subcutaneous injection of buserelin acetate, a potent synthetic GnRH analogue. The obtained data implied that hypothalamic neuroinflammation occurs during onset and/or peak of the disease in both sexes (upregulation of Gfap, Il1b, Il6, Ccl2 and Spp1 mRNA expression). However, hypothalamic Kiss1 and Gnrh mRNA expression was affected differently in males and females, as well as mRNA expression of pituitary signature genes - Lhb, Fshb and Gnrhr. LH levels drop transiently following the course of the disease; in females, this drop coincided with the arrest in diestrus. Nevertheless, the pituitary remained responsive to buserelin treatment. Our results indicate that EAE affects the regulation of hypothalamo-pituitary-gonadal axis in both sexes. Further analyses are needed to elucidate the causes and details of differences in hypothalamic response to neuroinflammation.
PB  - Belgrade: Faculty of Pharmacy
C3  - Abstract Book: 2nd Symposium in Biomedicine: Basic and Clinical Neuroscience; 2019 May 9; Belgrade, Serbia
T1  - Sex differences in the regulatory changes of HPG axis during experimental autoimmune encephalomyelitis in rats
SP  - 11
EP  - 12
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5979
ER  - 

@conference{
author = "Milošević, Ana and Janjić, Marija and Lavrnja, Irena and Peković, Sanja and Bjelobaba, Ivana",
year = "2019",
abstract = "Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease, two to three times more common in women than in men. Because the effects of neuroinflammation on the reproductive status have not been fully explored, our aim was to investigate the impact of experimental autoimmune encephalomyelitis (EAE), the rat model of MS, on hypothalamo-pituitary-gonadal axis. EAE was actively induced in Dark-Agouti rats of both sexes. The animals were examined daily for disease symptoms, weight changes, and estrous cycle phase. The animals were sacrificed at the onset, peak, and end of the disease. Hypothalamic and pituitary tissues were dissected for qRT-PCR analyses. Blood was collected for LH measurements. In separate experiments, groups of male and female animals at the peak of EAE and naïve controls received a subcutaneous injection of buserelin acetate, a potent synthetic GnRH analogue. The obtained data implied that hypothalamic neuroinflammation occurs during onset and/or peak of the disease in both sexes (upregulation of Gfap, Il1b, Il6, Ccl2 and Spp1 mRNA expression). However, hypothalamic Kiss1 and Gnrh mRNA expression was affected differently in males and females, as well as mRNA expression of pituitary signature genes - Lhb, Fshb and Gnrhr. LH levels drop transiently following the course of the disease; in females, this drop coincided with the arrest in diestrus. Nevertheless, the pituitary remained responsive to buserelin treatment. Our results indicate that EAE affects the regulation of hypothalamo-pituitary-gonadal axis in both sexes. Further analyses are needed to elucidate the causes and details of differences in hypothalamic response to neuroinflammation.",
publisher = "Belgrade: Faculty of Pharmacy",
journal = "Abstract Book: 2nd Symposium in Biomedicine: Basic and Clinical Neuroscience; 2019 May 9; Belgrade, Serbia",
title = "Sex differences in the regulatory changes of HPG axis during experimental autoimmune encephalomyelitis in rats",
pages = "11-12",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5979"
}

Milošević, A., Janjić, M., Lavrnja, I., Peković, S.,& Bjelobaba, I.. (2019). Sex differences in the regulatory changes of HPG axis during experimental autoimmune encephalomyelitis in rats. in Abstract Book: 2nd Symposium in Biomedicine: Basic and Clinical Neuroscience; 2019 May 9; Belgrade, Serbia
Belgrade: Faculty of Pharmacy., 11-12.
https://hdl.handle.net/21.15107/rcub_ibiss_5979

Milošević A, Janjić M, Lavrnja I, Peković S, Bjelobaba I. Sex differences in the regulatory changes of HPG axis during experimental autoimmune encephalomyelitis in rats. in Abstract Book: 2nd Symposium in Biomedicine: Basic and Clinical Neuroscience; 2019 May 9; Belgrade, Serbia. 2019;:11-12.
https://hdl.handle.net/21.15107/rcub_ibiss_5979 .

Milošević, Ana, Janjić, Marija, Lavrnja, Irena, Peković, Sanja, Bjelobaba, Ivana, "Sex differences in the regulatory changes of HPG axis during experimental autoimmune encephalomyelitis in rats" in Abstract Book: 2nd Symposium in Biomedicine: Basic and Clinical Neuroscience; 2019 May 9; Belgrade, Serbia (2019):11-12,
https://hdl.handle.net/21.15107/rcub_ibiss_5979 .