Title |
Neuroprotective arylpiperazine dopaminergic/serotonergic ligands suppress experimental autoimmune encephalomyelitis in rats
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Published in |
Journal of Neurochemistry, July 2015
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DOI | 10.1111/jnc.13198 |
Pubmed ID | |
Authors |
Marjan Popovic, Zeljka Stanojevic, Jelena Tosic, Aleksandra Isakovic, Verica Paunovic, Sasa Petricevic, Tamara Martinovic, Darko Ciric, Tamara Kravic-Stevovic, Vukic Soskic, Sladjana Kostic-Rajacic, Kaveh Shakib, Vladimir Bumbasirevic, Vladimir Trajkovic |
Abstract |
Arylpiperazine-based dopaminergic/serotonergic ligands exert neuroprotective activity. We examined the effect of arylpiperazine D2 /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 D2 and 5-HT1A receptors. The protection was retained if 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 TNF, IL-6, IL-1, and GM-CSF, TH 1 cytokine IFN-γ, TH 17 cytokine IL-17, as well as the signature transcription factors of TH 1 (T-bet) and TH 17 (RORγt) 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 protein-activated encephalitogenic T cells. In conclusion, arylpiperazine dopaminergic/serotonergic ligands suppress EAE through a direct neuroprotective action and decrease in CNS inflammation. This article is protected by copyright. All rights reserved. |
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Germany | 1 | 100% |
Demographic breakdown
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 30 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 8 | 27% |
Researcher | 4 | 13% |
Professor > Associate Professor | 2 | 7% |
Student > Doctoral Student | 2 | 7% |
Student > Bachelor | 1 | 3% |
Other | 6 | 20% |
Unknown | 7 | 23% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 6 | 20% |
Agricultural and Biological Sciences | 4 | 13% |
Neuroscience | 3 | 10% |
Biochemistry, Genetics and Molecular Biology | 2 | 7% |
Immunology and Microbiology | 1 | 3% |
Other | 4 | 13% |
Unknown | 10 | 33% |