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  - CONF
AU  - Živković, Anica
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Milošević, Katarina
AU  - Božić, Iva
AU  - Trifunović, Svetlana
AU  - Savić, Danijela
AU  - Bjelobaba, Ivana
AU  - Lavrnja, Irena
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5859
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
system (CNS) that leads to severe neurological deficits. In past decades, numerous
studies have observed that anterior pituitary hormones play a pivotal role in regulation
of physiological immune response, as well as development and course of autoimmune
diseases.
Specifically, growth hormone (GH) and prolactin (PRL), peptide hormones
synthesized and secreted by the anterior pituitary, have been implicated in regulating
the immune system. Growth hormone secretion is positively regulated by the
hypothalamic growth hormone-releasing hormone (GHRH), while somatostatin (SST)
inhibits the release of GH.
Previous studies demonstrated that GHRH and GH are implicated in development of
experimental autoimmune encephalomyelitis (EAE), a representative animal model of
MS. Significantly higher PRL serum levels in MS patients were also reported.
We investigated spatiotemporal differences in GH and PRL levels in pituitaries from
EAE animals. Using immunolabeling and stereological methods we evaluated changes
in volume density of GH- and PRL-positive cells in pituitary gland of animals with
EAE compared to healthy controls. As we determined that there is no change in cell
volume density, we checked if there are any changes in gene expression of PRL, GH,
as well as GHRH and SST. Growth hormone and prolactin protein expression was
also measured in anterior pituitary. Our results show that, in addition to GH- and
PRL-positive cells volume density, there are no significant changes in gene and
protein expression in anterior pituitary during EAE.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Growth hormone and prolactin gene expression and protein levels are not affected during EAE in rats
SP  - 105
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5859
ER  - 

@conference{
author = "Živković, Anica and Milošević, Ana and Janjić, Marija and Milošević, Katarina and Božić, Iva and Trifunović, Svetlana and Savić, Danijela and Bjelobaba, Ivana and Lavrnja, Irena",
year = "2023",
abstract = "Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
system (CNS) that leads to severe neurological deficits. In past decades, numerous
studies have observed that anterior pituitary hormones play a pivotal role in regulation
of physiological immune response, as well as development and course of autoimmune
diseases.
Specifically, growth hormone (GH) and prolactin (PRL), peptide hormones
synthesized and secreted by the anterior pituitary, have been implicated in regulating
the immune system. Growth hormone secretion is positively regulated by the
hypothalamic growth hormone-releasing hormone (GHRH), while somatostatin (SST)
inhibits the release of GH.
Previous studies demonstrated that GHRH and GH are implicated in development of
experimental autoimmune encephalomyelitis (EAE), a representative animal model of
MS. Significantly higher PRL serum levels in MS patients were also reported.
We investigated spatiotemporal differences in GH and PRL levels in pituitaries from
EAE animals. Using immunolabeling and stereological methods we evaluated changes
in volume density of GH- and PRL-positive cells in pituitary gland of animals with
EAE compared to healthy controls. As we determined that there is no change in cell
volume density, we checked if there are any changes in gene expression of PRL, GH,
as well as GHRH and SST. Growth hormone and prolactin protein expression was
also measured in anterior pituitary. Our results show that, in addition to GH- and
PRL-positive cells volume density, there are no significant changes in gene and
protein expression in anterior pituitary during EAE.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Growth hormone and prolactin gene expression and protein levels are not affected during EAE in rats",
pages = "105",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5859"
}

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

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

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

TY  - CONF
AU  - Milošević, Ana
AU  - Milošević, Katarina
AU  - Nikolić, Ljiljana
AU  - Bogdanović Pristov, Jelena
AU  - Božić, Iva
AU  - Živković, Anica
AU  - Lavrnja, Irena
AU  - Savić, Danijela
AU  - Janjić, Marija
AU  - Bjelobaba, Ivana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5836
AB  - Gonadotropin-releasing hormone (GnRH) is a hypothalamic decapeptide that controls
mammalian reproduction by acting on its receptor (GnRHR) expressed on pituitary
gonadotrope cells. While GnRHR signaling in gonadotropes is well described,
knowledge of GnRHR activation-related events at extrapituitary sites including
neurons is limited. It was proposed that GnRH analogs (GnRHa) induce distinct
changes in hippocampal gene expression, emotional processes, and cognitive
functions.
To explore neuronal GnRHR signaling we used the human neuroblastoma cell line
SH-SY5Y. Further, we explored the regional expression of Gnrhr in rat brain and
investigated the expression of several relevant genes in the hippocampus and preoptic
area of peripubertal male rats treated with GnRHa.
GNRHR is expressed in SH-SY5Y cell line, but its expression does not change after
adding GnRHa in the incubation media. Electrophysiological recordings confirmed
that GnRHa induced membrane depolarization but could not evoke action potentials.
In the rat brain, Gnrhr expression could be detected in the hippocampus, amygdala,
and hypothalamus, including the preoptic area. Prolonged treatment of peripubertal
rats with GnRHa had no effect on the expression of genes in the hippocampus
previously shown to be affected in the sheep model of delayed puberty.
These results imply that neuronal GnRHR is either differently coupled (not coupled
with Gq/11 protein), or that its membrane density is too low to induce transcriptional
events. More investigation is needed to elucidate the role(s) of GnRH-GnRHR
signaling in the brain.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - GnRHR signaling in neuronal cells: in vitro and in vivo data
SP  - 53
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5836
ER  - 

@conference{
author = "Milošević, Ana and Milošević, Katarina and Nikolić, Ljiljana and Bogdanović Pristov, Jelena and Božić, Iva and Živković, Anica and Lavrnja, Irena and Savić, Danijela and Janjić, Marija and Bjelobaba, Ivana",
year = "2023",
abstract = "Gonadotropin-releasing hormone (GnRH) is a hypothalamic decapeptide that controls
mammalian reproduction by acting on its receptor (GnRHR) expressed on pituitary
gonadotrope cells. While GnRHR signaling in gonadotropes is well described,
knowledge of GnRHR activation-related events at extrapituitary sites including
neurons is limited. It was proposed that GnRH analogs (GnRHa) induce distinct
changes in hippocampal gene expression, emotional processes, and cognitive
functions.
To explore neuronal GnRHR signaling we used the human neuroblastoma cell line
SH-SY5Y. Further, we explored the regional expression of Gnrhr in rat brain and
investigated the expression of several relevant genes in the hippocampus and preoptic
area of peripubertal male rats treated with GnRHa.
GNRHR is expressed in SH-SY5Y cell line, but its expression does not change after
adding GnRHa in the incubation media. Electrophysiological recordings confirmed
that GnRHa induced membrane depolarization but could not evoke action potentials.
In the rat brain, Gnrhr expression could be detected in the hippocampus, amygdala,
and hypothalamus, including the preoptic area. Prolonged treatment of peripubertal
rats with GnRHa had no effect on the expression of genes in the hippocampus
previously shown to be affected in the sheep model of delayed puberty.
These results imply that neuronal GnRHR is either differently coupled (not coupled
with Gq/11 protein), or that its membrane density is too low to induce transcriptional
events. More investigation is needed to elucidate the role(s) of GnRH-GnRHR
signaling in the brain.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "GnRHR signaling in neuronal cells: in vitro and in vivo data",
pages = "53",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5836"
}

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

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

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