Chronic nicotine treatment decreases LPS signaling through NF-kappa B and TLR-4 modulation in the hippocampus

Autor(es)

Cafe-Mendes, Cecilia Cerqueira ; Garay-Malpartida, Humberto Miguel ; Malta, Marilia Brinati ; Lima, Larrissa de Sa ; Scavone, Cristoforo ; Ferreira, Zulma S. ; Markus, Regina P. ; Marcourakis, Tania

• Tipo de documento: Artigo Científico
• Fonte: Neuroscience Letters; v. 636, p. 7-pg., 2017-01-01.

Resumo

The hippocampus is a brain region that is rich in nicotinic acetylcholine receptors (nAChRs), especially the alpha 7 subtype. The hippocampus is severely affected in disorders that have a neuroinflammatory component, such as Alzheimer's disease, Parkinson's disease, and schizophrenia. Previous studies demonstrated both in vivo and in vitro that nicotine inhibits immunological responses, including those that are triggered by the inflammatory agent lipopolysaccharide (LPS), the endotoxin of Gram-negative bacteria. The present study investigated whether chronically administered nicotine interferes with the nuclear binding of nuclear factor-kappa B (NF-kappa B) and the expression of LPS-induced inflammatory response genes. The results indicated that chronic nicotine administration (0.1 mg/kg, s.c., 14 days) inhibited the LPS-induced nuclear binding of NF-kappa B and mRNA expression levels of Tnf, Il1b, Nos2, and Tlr4. The presence of both the selective 7 nAChR antagonist methyllycaconitine (MLA; 5.0 mg/kg i.p., 14 days) and the nonselective nAChR antagonist mecamylamine (Meca; 1.0 mg/kg, s.c., 14 days) reversed the inhibitory effects of nicotine. These results suggest that the chronic activation of alpha 7- and alpha(x)beta(y)-containing nAChRs reduces acute inflammatory responses in the brain. (C) 2016 Published by Elsevier Ireland Ltd. (AU)

• Processo FAPESP: 06/58924-0 - Efeito da nicotina na ativacao do fator de transcricao nf-kb no sistema nervoso central na vigencia de estimulo inflamatorio induzido por lipopolissacarideo.
• Beneficiário: Tania Marcourakis
• Modalidade de apoio: Auxílio à Pesquisa - Regular