CER - Central Repository
Institute of Chemistry, Technology and Metallurgy
    • English
    • Српски
    • Српски (Serbia)
  • English 
    • English
    • Serbian (Cyrilic)
    • Serbian (Latin)
  • Login
View Item 
  •   Central Repository
  • IHTM
  • Radovi istraživača / Researchers' publications
  • View Item
  •   Central Repository
  • IHTM
  • Radovi istraživača / Researchers' publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats

Thumbnail
2015
1810.pdf (1.498Mb)
Authors
Popović, Marjan
Stanojević, Željka
Tosic, Jelena
Isaković, Aleksandra
Paunović, Verica
Petricevic, Sasa
Martinovic, Tamara
Ciric, Darko
Kravić-Stevović, Tamara
Šoškić, Vukić
Kostić Rajačić, Slađana
Shakib, Kaveh
Bumbasirevic, Vladimir
Trajković, Vladimir
Article (Published version)
Metadata
Show full item record
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.

Keywords:
apoptosis / arylpiperazines / CNS inflammation / neuroprotection / oligodendrocytes
Source:
Journal of Neurochemistry, 2015, 135, 1, 125-138
Publisher:
  • Wiley, Hoboken
Projects:
  • Modulation of intracellular energy balance-controlling signalling pathways in therapy of cancer and neuro-immuno-endocrine disorders (RS-41025)
  • ProteoSysAG (Mainz, Germany)

DOI: 10.1111/jnc.13198

ISSN: 0022-3042

PubMed: 26083644

WoS: 000362828000012

Scopus: 2-s2.0-84942423493
[ Google Scholar ]
10
10
URI
http://cer.ihtm.bg.ac.rs/handle/123456789/1812
Collections
  • Radovi istraživača / Researchers' publications
Institution
IHTM

DSpace software copyright © 2002-2015  DuraSpace
About CeR – Central Repository | Send Feedback

OpenAIRERCUB
 

 

All of DSpaceInstitutionsAuthorsTitlesSubjectsThis institutionAuthorsTitlesSubjects

Statistics

View Usage Statistics

DSpace software copyright © 2002-2015  DuraSpace
About CeR – Central Repository | Send Feedback

OpenAIRERCUB