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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TY  - 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  - 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  - Jakovljević, Marija
AU  - Lavrnja, Irena
AU  - Božić, Iva
AU  - Milošević, Ana
AU  - Bjelobaba, Ivana
AU  - Savić, Danijela
AU  - Sévigny, Jean
AU  - Peković, Sanja
AU  - Nedeljković, Nadežda
AU  - Laketa, Danijela
PY  - 2019
UR  - https://www.frontiersin.org/article/10.3389/fnins.2019.00410/full
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6498900
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3434
AB  - Purinergic signaling is critically involved in neuroinflammation associated with multiple sclerosis (MS) and its major inflammatory animal model, experimental autoimmune encephalomyelitis (EAE). Herein, we explored the expression of ectonucleoside triphosphate diphosphohydrolase1 (NTPDase1/CD39) in the spinal cord, at the onset (Eo), peak (Ep), and end (Ee) of EAE. Several-fold increase in mRNA and in NTPDase1 protein levels were observed at Eo and Ep. In situ hybridization combined with fluorescent immunohistochemistry showed that reactive microglia and infiltrated mononuclear cells mostly accounted for the observed increase. Colocalization analysis revealed that up to 80% of Iba1 immunoreactivity and ∼50% of CD68 immunoreactivity was colocalized with NTPDase1, while flow cytometric analysis revealed that ∼70% of mononuclear infiltrates were NTPDase1+ at Ep. Given the main role of NTPDase1 to degrade proinflammatory ATP, we hypothesized that the observed up-regulation of NTPDase1 may be associated with the transition between proinflammatory M1-like to neuroprotective M2-like phenotype of microglia/macrophages during EAE. Functional phenotype of reactive microglia/macrophages that overexpress NTPDase1 was assessed by multi-image colocalization analysis using iNOS and Arg1 as selective markers for M1 and M2 reactive states, respectively. At the peak of EAE NTPDase1 immunoreactivity showed much higher co-occurrence with Arg1 immunoreactivity in microglia and macrophages, compared to iNOS, implying its stronger association with M2-like reactive phenotype. Additionally, in ∼80% of CD68 positive cells NTPDase1 was coexpressed with Arg1 compared to negligible fraction coexpresing iNOS and ∼15% coexpresing both markers, additionally indicating prevalent association of NTPDase1 with M2-like microglial/macrophages phenotype at Ep. Together, our data suggest an association between NTPDase1 up-regulation by reactive microglia and infiltrated macrophages and their transition toward antiinflammatory phenotype in EAE.
T2  - Frontiers in Neuroscience
T1  - Induction of NTPDase1/CD39 by Reactive Microglia and Macrophages Is Associated With the Functional State During EAE.
VL  - 13
DO  - 10.3389/fnins.2019.00410
SP  - 410
ER  - 

@article{
author = "Jakovljević, Marija and Lavrnja, Irena and Božić, Iva and Milošević, Ana and Bjelobaba, Ivana and Savić, Danijela and Sévigny, Jean and Peković, Sanja and Nedeljković, Nadežda and Laketa, Danijela",
year = "2019",
abstract = "Purinergic signaling is critically involved in neuroinflammation associated with multiple sclerosis (MS) and its major inflammatory animal model, experimental autoimmune encephalomyelitis (EAE). Herein, we explored the expression of ectonucleoside triphosphate diphosphohydrolase1 (NTPDase1/CD39) in the spinal cord, at the onset (Eo), peak (Ep), and end (Ee) of EAE. Several-fold increase in mRNA and in NTPDase1 protein levels were observed at Eo and Ep. In situ hybridization combined with fluorescent immunohistochemistry showed that reactive microglia and infiltrated mononuclear cells mostly accounted for the observed increase. Colocalization analysis revealed that up to 80% of Iba1 immunoreactivity and ∼50% of CD68 immunoreactivity was colocalized with NTPDase1, while flow cytometric analysis revealed that ∼70% of mononuclear infiltrates were NTPDase1+ at Ep. Given the main role of NTPDase1 to degrade proinflammatory ATP, we hypothesized that the observed up-regulation of NTPDase1 may be associated with the transition between proinflammatory M1-like to neuroprotective M2-like phenotype of microglia/macrophages during EAE. Functional phenotype of reactive microglia/macrophages that overexpress NTPDase1 was assessed by multi-image colocalization analysis using iNOS and Arg1 as selective markers for M1 and M2 reactive states, respectively. At the peak of EAE NTPDase1 immunoreactivity showed much higher co-occurrence with Arg1 immunoreactivity in microglia and macrophages, compared to iNOS, implying its stronger association with M2-like reactive phenotype. Additionally, in ∼80% of CD68 positive cells NTPDase1 was coexpressed with Arg1 compared to negligible fraction coexpresing iNOS and ∼15% coexpresing both markers, additionally indicating prevalent association of NTPDase1 with M2-like microglial/macrophages phenotype at Ep. Together, our data suggest an association between NTPDase1 up-regulation by reactive microglia and infiltrated macrophages and their transition toward antiinflammatory phenotype in EAE.",
journal = "Frontiers in Neuroscience",
title = "Induction of NTPDase1/CD39 by Reactive Microglia and Macrophages Is Associated With the Functional State During EAE.",
volume = "13",
doi = "10.3389/fnins.2019.00410",
pages = "410"
}

Jakovljević, M., Lavrnja, I., Božić, I., Milošević, A., Bjelobaba, I., Savić, D., Sévigny, J., Peković, S., Nedeljković, N.,& Laketa, D.. (2019). Induction of NTPDase1/CD39 by Reactive Microglia and Macrophages Is Associated With the Functional State During EAE.. in Frontiers in Neuroscience, 13, 410.
https://doi.org/10.3389/fnins.2019.00410

Jakovljević M, Lavrnja I, Božić I, Milošević A, Bjelobaba I, Savić D, Sévigny J, Peković S, Nedeljković N, Laketa D. Induction of NTPDase1/CD39 by Reactive Microglia and Macrophages Is Associated With the Functional State During EAE.. in Frontiers in Neuroscience. 2019;13:410.
doi:10.3389/fnins.2019.00410 .

Jakovljević, Marija, Lavrnja, Irena, Božić, Iva, Milošević, Ana, Bjelobaba, Ivana, Savić, Danijela, Sévigny, Jean, Peković, Sanja, Nedeljković, Nadežda, Laketa, Danijela, "Induction of NTPDase1/CD39 by Reactive Microglia and Macrophages Is Associated With the Functional State During EAE." in Frontiers in Neuroscience, 13 (2019):410,
https://doi.org/10.3389/fnins.2019.00410 . .

TY  - JOUR
AU  - Božić, Iva
AU  - Milošević, Katarina
AU  - Laketa, Danijela
AU  - Adžić, Marija
AU  - Jakovljević, Marija
AU  - Bjelobaba, Ivana
AU  - Savić, Danijela
AU  - Nedeljković, Nadežda
AU  - Peković, Sanja
AU  - Lavrnja, Irena
PY  - 2018
UR  - http://link.springer.com/10.1007/s11064-018-2509-8
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3027
AB  - Kv1.3 is a voltage gated potassium channel that has been implicated in pathophysiology of multiple sclerosis (MS). In the present study we investigated temporal and cellular expression pattern of this channel in the lumbar part of spinal cords of animals with experimental autoimmune encephalomyelitis (EAE), animal model of MS. EAE was actively induced in female Dark Agouti rats. Expression of Kv1.3 was analyzed at different time points of disease progression, at the onset, peak and end of EAE. We here show that Kv1.3 increased by several folds at the peak of EAE at both gene and protein level. Double immunofluorescence analyses demonstrated localization of Kv1.3 on activated microglia, macrophages, and reactive astrocytes around inflammatory lesions. In vitro experiments showed that pharmacological block of Kv1.3 in activated astrocytes suppresses the expression of proinflammatory mediators, suggesting a role of this channel in inflammation. Our results support the hypothesis that Kv1.3 may be a therapeutic target of interest for MS and add astrocytes to the list of cells whose activation would be suppressed by inhibiting Kv1.3 in inflammatory conditions.
T2  - Neurochemical Research
T1  - Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis.
IS  - 5
VL  - 43
DO  - 10.1007/s11064-018-2509-8
SP  - 1020
EP  - 1034
ER  - 

@article{
author = "Božić, Iva and Milošević, Katarina and Laketa, Danijela and Adžić, Marija and Jakovljević, Marija and Bjelobaba, Ivana and Savić, Danijela and Nedeljković, Nadežda and Peković, Sanja and Lavrnja, Irena",
year = "2018",
abstract = "Kv1.3 is a voltage gated potassium channel that has been implicated in pathophysiology of multiple sclerosis (MS). In the present study we investigated temporal and cellular expression pattern of this channel in the lumbar part of spinal cords of animals with experimental autoimmune encephalomyelitis (EAE), animal model of MS. EAE was actively induced in female Dark Agouti rats. Expression of Kv1.3 was analyzed at different time points of disease progression, at the onset, peak and end of EAE. We here show that Kv1.3 increased by several folds at the peak of EAE at both gene and protein level. Double immunofluorescence analyses demonstrated localization of Kv1.3 on activated microglia, macrophages, and reactive astrocytes around inflammatory lesions. In vitro experiments showed that pharmacological block of Kv1.3 in activated astrocytes suppresses the expression of proinflammatory mediators, suggesting a role of this channel in inflammation. Our results support the hypothesis that Kv1.3 may be a therapeutic target of interest for MS and add astrocytes to the list of cells whose activation would be suppressed by inhibiting Kv1.3 in inflammatory conditions.",
journal = "Neurochemical Research",
title = "Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis.",
number = "5",
volume = "43",
doi = "10.1007/s11064-018-2509-8",
pages = "1020-1034"
}

Božić, I., Milošević, K., Laketa, D., Adžić, M., Jakovljević, M., Bjelobaba, I., Savić, D., Nedeljković, N., Peković, S.,& Lavrnja, I.. (2018). Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis.. in Neurochemical Research, 43(5), 1020-1034.
https://doi.org/10.1007/s11064-018-2509-8

Božić I, Milošević K, Laketa D, Adžić M, Jakovljević M, Bjelobaba I, Savić D, Nedeljković N, Peković S, Lavrnja I. Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis.. in Neurochemical Research. 2018;43(5):1020-1034.
doi:10.1007/s11064-018-2509-8 .

Božić, Iva, Milošević, Katarina, Laketa, Danijela, Adžić, Marija, Jakovljević, Marija, Bjelobaba, Ivana, Savić, Danijela, Nedeljković, Nadežda, Peković, Sanja, Lavrnja, Irena, "Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis." in Neurochemical Research, 43, no. 5 (2018):1020-1034,
https://doi.org/10.1007/s11064-018-2509-8 . .

TY  - CONF
AU  - Savić, Danijela
AU  - Lavrnja, Irena
AU  - Bjelobaba, Ivana
AU  - Dacić, Sanja
AU  - Laketa, Danijela
AU  - Božić, Iva
AU  - Jakovljević, Marija
AU  - Nedeljković, Nadežda
AU  - Rakić, Ljubisav
AU  - Peković, Sanja
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5888
AB  - Ribavirin je purinski nukleozidni analog, otkriven pre više decenija i odobren kao lek protiv virusa hepatitisa C. Sa otkrićem direktnih antivirusnih agenasa, nastupila je revolucija u lečenju hepatitisa C, a terapijska uloga ribavirina je marginalizovana. Međutim, ribavirin ima širok spektar dejstva što je otvorilo mogućnost da se ovaj lek preusmeri ka tretmanu drugih oboljenja. Naime, osim što deluje antivirusno (inhibicija virusne RNK polimeraze i izazivanje letalne mutageneze) ribavirin je i inhibitor eukariotskog faktora za inicijaciju translacije e4E, što je zaslužno za njegov anti-tumorski efekat, pokazan u leukemiji i na ćelijama glioma. Njegova druga opšte poznata unutarćelijska meta jeste enzim inozin-5’-monofosfat dehidrogenaza (IMPDH), koji predstavlja ključni faktor u de novo sintezi guaninskih nukleotida. Ćelije koje se isključivo na ovaj način snabdevaju purinskim nukleotidima, kao što su aktivirani limfociti i neke proliferišuće ćelije, izuzetno su senzitivne na delovanje ribavirina. Inhibicija IMPDH odgovorna je za imunosupresivno i imunomodulatorno dejstvo ribavirina, pokazano u in vitro i in vivo modelima neuroinflamacije. Dakle, iako ribavirin gubi centralnu ulogu koju je imao u terapiji infekcije virusom hepatitisa C, njegova multipotentna priroda koja se ogleda u različitim mehanizmima delovanja, predstavlja potencijal za preusmeravanje ka novim terapijskim indikacijama, kao što su kancer ili multipla skleroza.
PB  - Belgrade: Serbian Biological Society
C3  - Drugi kongres biologa Srbije; 2018 Sep 25-30; Kladovo, Srbija
T1  - Preusmeravanje antivirusnog leka ribavirina ka novim terapijskim indikacijama: primer multiple skleroze i neoplastičnih transformacija
SP  - 146
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5888
ER  - 

@conference{
author = "Savić, Danijela and Lavrnja, Irena and Bjelobaba, Ivana and Dacić, Sanja and Laketa, Danijela and Božić, Iva and Jakovljević, Marija and Nedeljković, Nadežda and Rakić, Ljubisav and Peković, Sanja",
year = "2018",
abstract = "Ribavirin je purinski nukleozidni analog, otkriven pre više decenija i odobren kao lek protiv virusa hepatitisa C. Sa otkrićem direktnih antivirusnih agenasa, nastupila je revolucija u lečenju hepatitisa C, a terapijska uloga ribavirina je marginalizovana. Međutim, ribavirin ima širok spektar dejstva što je otvorilo mogućnost da se ovaj lek preusmeri ka tretmanu drugih oboljenja. Naime, osim što deluje antivirusno (inhibicija virusne RNK polimeraze i izazivanje letalne mutageneze) ribavirin je i inhibitor eukariotskog faktora za inicijaciju translacije e4E, što je zaslužno za njegov anti-tumorski efekat, pokazan u leukemiji i na ćelijama glioma. Njegova druga opšte poznata unutarćelijska meta jeste enzim inozin-5’-monofosfat dehidrogenaza (IMPDH), koji predstavlja ključni faktor u de novo sintezi guaninskih nukleotida. Ćelije koje se isključivo na ovaj način snabdevaju purinskim nukleotidima, kao što su aktivirani limfociti i neke proliferišuće ćelije, izuzetno su senzitivne na delovanje ribavirina. Inhibicija IMPDH odgovorna je za imunosupresivno i imunomodulatorno dejstvo ribavirina, pokazano u in vitro i in vivo modelima neuroinflamacije. Dakle, iako ribavirin gubi centralnu ulogu koju je imao u terapiji infekcije virusom hepatitisa C, njegova multipotentna priroda koja se ogleda u različitim mehanizmima delovanja, predstavlja potencijal za preusmeravanje ka novim terapijskim indikacijama, kao što su kancer ili multipla skleroza.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Drugi kongres biologa Srbije; 2018 Sep 25-30; Kladovo, Srbija",
title = "Preusmeravanje antivirusnog leka ribavirina ka novim terapijskim indikacijama: primer multiple skleroze i neoplastičnih transformacija",
pages = "146",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5888"
}

Savić, D., Lavrnja, I., Bjelobaba, I., Dacić, S., Laketa, D., Božić, I., Jakovljević, M., Nedeljković, N., Rakić, L.,& Peković, S.. (2018). Preusmeravanje antivirusnog leka ribavirina ka novim terapijskim indikacijama: primer multiple skleroze i neoplastičnih transformacija. in Drugi kongres biologa Srbije; 2018 Sep 25-30; Kladovo, Srbija
Belgrade: Serbian Biological Society., 146.
https://hdl.handle.net/21.15107/rcub_ibiss_5888

Savić D, Lavrnja I, Bjelobaba I, Dacić S, Laketa D, Božić I, Jakovljević M, Nedeljković N, Rakić L, Peković S. Preusmeravanje antivirusnog leka ribavirina ka novim terapijskim indikacijama: primer multiple skleroze i neoplastičnih transformacija. in Drugi kongres biologa Srbije; 2018 Sep 25-30; Kladovo, Srbija. 2018;:146.
https://hdl.handle.net/21.15107/rcub_ibiss_5888 .

Savić, Danijela, Lavrnja, Irena, Bjelobaba, Ivana, Dacić, Sanja, Laketa, Danijela, Božić, Iva, Jakovljević, Marija, Nedeljković, Nadežda, Rakić, Ljubisav, Peković, Sanja, "Preusmeravanje antivirusnog leka ribavirina ka novim terapijskim indikacijama: primer multiple skleroze i neoplastičnih transformacija" in Drugi kongres biologa Srbije; 2018 Sep 25-30; Kladovo, Srbija (2018):146,
https://hdl.handle.net/21.15107/rcub_ibiss_5888 .

TY  - JOUR
AU  - Jakovljević, Marija
AU  - Lavrnja, Irena
AU  - Božić, Iva
AU  - Savić, Danijela
AU  - Bjelobaba, Ivana
AU  - Peković, Sanja
AU  - Sévigny, Jean
AU  - Nedeljković, Nadežda
AU  - Laketa, Danijela
PY  - 2017
UR  - http://journal.frontiersin.org/article/10.3389/fncel.2017.00333/full
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5670145
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3152
AB  - The present study explores tissue and cellular distribution of ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2) and the gene and protein expression in rat spinal cord during the course of experimental autoimmune encephalomyelitis (EAE). Given that NTPDase2 hydrolyzes ATP with a transient accumulation of ADP, the expression of ADP-sensitive P2 purinoceptors was analyzed as well. The autoimmune disease was actively induced in Dark Agouti female rats and the changes were analyzed 10, 15 and 29 days after the induction. These selected time points correspond to the onset ( Eo ), peak ( Ep ) and recovery ( Er ) from EAE. In control animals, NTPDase2 was confined in the white matter, in most of the glial fibrillary acidic protein (GFAP)-immunoreactive (ir) astrocytes and in a considerable number of nestin-ir cells, while the other cell types were immunonegative. Immunoreactivity corresponding to NTPDase2 decreased significantly at Eo and Ep and then returned to the baseline levels at Er . The preservation of the proportion of GFAP single-labeled and GFAP/NTPDase2 double-labeled elements along the course of EAE indicated that changes in NTPDase2-ir occurred at fibrous astrocytes that typically express NTPDase2 in normal conditions. Significant downregulation of P2Y1 and P2Y12 receptor proteins at Eo and several-fold induction of P2Y12 and P2Y13 receptor proteins at Ep and/or Er were observed implying that the pathophysiological process in EAE may be linked to ADP signaling. Cell-surface expression of NTPDase2, NTPDase1/CD39 and ecto-5'-nucleotidase (eN/CD73) was analyzed in CD4+ T cells of a draining lymph node by fluorescence-activated cell sorting. The induction of EAE was associated with a transient decrease in a number of CD4+ NTPDase2+ T cells in a draining lymph node, whereas the recovery was characterized by an increase in NTPDase2+ cells in both CD4+ and CD4- cell populations. The opposite was found for NTPDase1/CD39+ and eN/CD73+ cells, which slightly increased in number with progression of the disease, particularly in CD4- cells, and then decreased in the recovery. Finally, CD4+ NTPDase2+ cells were never observed in the spinal cord parenchyma. Taken together, our results suggest that the process of neuroinflammation in EAE may be associated with altered ADP signaling.
T2  - Frontiers in Cellular Neuroscience
T1  - Down-regulation of NTPDase2 and ADP-sensitive P2 Purinoceptors Correlate with Severity of Symptoms during Experimental Autoimmune Encephalomyelitis.
VL  - 11
DO  - 10.3389/fncel.2017.00333
SP  - 333
ER  - 

@article{
author = "Jakovljević, Marija and Lavrnja, Irena and Božić, Iva and Savić, Danijela and Bjelobaba, Ivana and Peković, Sanja and Sévigny, Jean and Nedeljković, Nadežda and Laketa, Danijela",
year = "2017",
abstract = "The present study explores tissue and cellular distribution of ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2) and the gene and protein expression in rat spinal cord during the course of experimental autoimmune encephalomyelitis (EAE). Given that NTPDase2 hydrolyzes ATP with a transient accumulation of ADP, the expression of ADP-sensitive P2 purinoceptors was analyzed as well. The autoimmune disease was actively induced in Dark Agouti female rats and the changes were analyzed 10, 15 and 29 days after the induction. These selected time points correspond to the onset ( Eo ), peak ( Ep ) and recovery ( Er ) from EAE. In control animals, NTPDase2 was confined in the white matter, in most of the glial fibrillary acidic protein (GFAP)-immunoreactive (ir) astrocytes and in a considerable number of nestin-ir cells, while the other cell types were immunonegative. Immunoreactivity corresponding to NTPDase2 decreased significantly at Eo and Ep and then returned to the baseline levels at Er . The preservation of the proportion of GFAP single-labeled and GFAP/NTPDase2 double-labeled elements along the course of EAE indicated that changes in NTPDase2-ir occurred at fibrous astrocytes that typically express NTPDase2 in normal conditions. Significant downregulation of P2Y1 and P2Y12 receptor proteins at Eo and several-fold induction of P2Y12 and P2Y13 receptor proteins at Ep and/or Er were observed implying that the pathophysiological process in EAE may be linked to ADP signaling. Cell-surface expression of NTPDase2, NTPDase1/CD39 and ecto-5'-nucleotidase (eN/CD73) was analyzed in CD4+ T cells of a draining lymph node by fluorescence-activated cell sorting. The induction of EAE was associated with a transient decrease in a number of CD4+ NTPDase2+ T cells in a draining lymph node, whereas the recovery was characterized by an increase in NTPDase2+ cells in both CD4+ and CD4- cell populations. The opposite was found for NTPDase1/CD39+ and eN/CD73+ cells, which slightly increased in number with progression of the disease, particularly in CD4- cells, and then decreased in the recovery. Finally, CD4+ NTPDase2+ cells were never observed in the spinal cord parenchyma. Taken together, our results suggest that the process of neuroinflammation in EAE may be associated with altered ADP signaling.",
journal = "Frontiers in Cellular Neuroscience",
title = "Down-regulation of NTPDase2 and ADP-sensitive P2 Purinoceptors Correlate with Severity of Symptoms during Experimental Autoimmune Encephalomyelitis.",
volume = "11",
doi = "10.3389/fncel.2017.00333",
pages = "333"
}

Jakovljević, M., Lavrnja, I., Božić, I., Savić, D., Bjelobaba, I., Peković, S., Sévigny, J., Nedeljković, N.,& Laketa, D.. (2017). Down-regulation of NTPDase2 and ADP-sensitive P2 Purinoceptors Correlate with Severity of Symptoms during Experimental Autoimmune Encephalomyelitis.. in Frontiers in Cellular Neuroscience, 11, 333.
https://doi.org/10.3389/fncel.2017.00333

Jakovljević M, Lavrnja I, Božić I, Savić D, Bjelobaba I, Peković S, Sévigny J, Nedeljković N, Laketa D. Down-regulation of NTPDase2 and ADP-sensitive P2 Purinoceptors Correlate with Severity of Symptoms during Experimental Autoimmune Encephalomyelitis.. in Frontiers in Cellular Neuroscience. 2017;11:333.
doi:10.3389/fncel.2017.00333 .

Jakovljević, Marija, Lavrnja, Irena, Božić, Iva, Savić, Danijela, Bjelobaba, Ivana, Peković, Sanja, Sévigny, Jean, Nedeljković, Nadežda, Laketa, Danijela, "Down-regulation of NTPDase2 and ADP-sensitive P2 Purinoceptors Correlate with Severity of Symptoms during Experimental Autoimmune Encephalomyelitis." in Frontiers in Cellular Neuroscience, 11 (2017):333,
https://doi.org/10.3389/fncel.2017.00333 . .