Show simple item record

dc.creatorPopović, Marjan
dc.creatorStanojević, Željka
dc.creatorTosic, Jelena
dc.creatorIsaković, Aleksandra
dc.creatorPaunović, Verica
dc.creatorPetricevic, Sasa
dc.creatorMartinovic, Tamara
dc.creatorCiric, Darko
dc.creatorKravić-Stevović, Tamara
dc.creatorŠoškić, Vukić
dc.creatorKostić Rajačić, Slađana
dc.creatorShakib, Kaveh
dc.creatorBumbasirevic, Vladimir
dc.creatorTrajković, Vladimir
dc.date.accessioned2019-01-30T17:47:29Z
dc.date.available2019-01-30T17:47:29Z
dc.date.issued2015
dc.identifier.issn0022-3042
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/1812
dc.description.abstractArylpiperazine-based dopaminergic/serotonergic ligands exert neuroprotective activity. We examined the effect of arylpiperazine D-2/5-HT1A ligands, N-{4-[2-(4-phenyl-piperazin-1-yl)-ethyl}-phenyl]- picolinamide (6a) and N-{3-[2-(4-phenyl-piperazin-1-yl)ethyl]- phenyl}-picolinamide (6b), in experimental autoimmune encephalomyelitis (EAE), a model of neuroinflammation. Both compounds (10 mg/kg i.p.) reduced EAE clinical signs in spinal cord homogenate-immunized Dark Agouti rats. Compound 6b was more efficient in delaying the disease onset and reducing the maximal clinical score, which correlated with its higher affinity for D-2 and 5-HT1A receptors. The protectionwas retainedif treatment was limited to the effector (from day 8 onwards), but not the induction phase (day 0-7) of EAE. Compound 6b reduced CNS immune infiltration and expression of mRNA encoding the proinflammatory cytokines tumor necrosis factor, IL-6, IL-1, and GM-CSF, T(H)1 cytokine IFN-gamma, T(H)17 cytokine IL-17, as well as the signature transcription factors of T(H)1 (T-bet) and T(H)17 (ROR gamma t) cells. Arylpiperazine treatment reduced apoptosis and increased the activation of anti-apoptotic mediators Akt and p70S6 kinase in the CNS of EAE animals. The in vitro treatment with 6b protected oligodendrocyte cell line OLN-93 and neuronal cell line PC12 from mitogen-activated normal T cells or myelin basic proteinactivated encephalitogenic T cells. In conclusion, arylpiperazine dopaminergic/serotonergic ligands suppress EAE through a direct neuroprotective action and decrease inCNS inflammation.en
dc.publisherWiley, Hoboken
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41025/RS//
dc.relationProteoSysAG (Mainz, Germany)
dc.rightsopenAccess
dc.sourceJournal of Neurochemistry
dc.subjectapoptosisen
dc.subjectarylpiperazinesen
dc.subjectCNS inflammationen
dc.subjectneuroprotectionen
dc.subjectoligodendrocytesen
dc.titleNeuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in ratsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractПауновић, Верица; Соскиц, Вукиц; Исаковиц, Aлександра; Схакиб, Кавех; Трајковиц, Владимир; Поповиц, Марјан; Станојевиц, Зељка; Тосиц, Јелена; Петрицевиц, Саса; Цириц, Дарко; Кравиц-Стевовиц, Тамара; Бумбасиревиц, Владимир; Мартиновиц, Тамара; Костић Рајачић, Слађана;
dc.citation.volume135
dc.citation.issue1
dc.citation.spage125
dc.citation.epage138
dc.citation.other135(1): 125-138
dc.citation.rankM21
dc.identifier.pmid26083644
dc.identifier.doi10.1111/jnc.13198
dc.identifier.rcubConv_3427
dc.identifier.fulltexthttp://cer.ihtm.bg.ac.rs//bitstream/id/8253/1810.pdf
dc.identifier.scopus2-s2.0-84942423493
dc.identifier.wos000362828000012
dc.type.versionpublishedVersion


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record