Prikaz osnovnih podataka o dokumentu
Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats
dc.creator | Popović, Marjan | |
dc.creator | Stanojević, Željka | |
dc.creator | Tosic, Jelena | |
dc.creator | Isaković, Aleksandra | |
dc.creator | Paunović, Verica | |
dc.creator | Petricevic, Sasa | |
dc.creator | Martinović, Tamara | |
dc.creator | Ciric, Darko | |
dc.creator | Kravić-Stevović, Tamara | |
dc.creator | Šoškić, Vukić | |
dc.creator | Kostić Rajačić, Slađana | |
dc.creator | Shakib, Kaveh | |
dc.creator | Bumbasirevic, Vladimir | |
dc.creator | Trajković, Vladimir | |
dc.date.accessioned | 2019-01-30T17:47:29Z | |
dc.date.available | 2019-01-30T17:47:29Z | |
dc.date.issued | 2015 | |
dc.identifier.issn | 0022-3042 | |
dc.identifier.uri | https://cer.ihtm.bg.ac.rs/handle/123456789/1812 | |
dc.description.abstract | Arylpiperazine-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.publisher | Wiley, Hoboken | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41025/RS// | |
dc.relation | ProteoSysAG (Mainz, Germany) | |
dc.rights | openAccess | |
dc.source | Journal of Neurochemistry | |
dc.subject | apoptosis | en |
dc.subject | arylpiperazines | en |
dc.subject | CNS inflammation | en |
dc.subject | neuroprotection | en |
dc.subject | oligodendrocytes | en |
dc.title | Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats | en |
dc.type | article | |
dc.rights.license | ARR | |
dcterms.abstract | Пауновић, 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.volume | 135 | |
dc.citation.issue | 1 | |
dc.citation.spage | 125 | |
dc.citation.epage | 138 | |
dc.citation.other | 135(1): 125-138 | |
dc.citation.rank | M21 | |
dc.identifier.pmid | 26083644 | |
dc.identifier.doi | 10.1111/jnc.13198 | |
dc.identifier.fulltext | https://cer.ihtm.bg.ac.rs//bitstream/id/8253/1810.pdf | |
dc.identifier.scopus | 2-s2.0-84942423493 | |
dc.identifier.wos | 000362828000012 | |
dc.type.version | publishedVersion |