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

• Published in: Neuroscience letters 2017-01, Vol.636, p.218-224
• Main Authors: Café-Mendes, Cecília Cerqueira, Garay-Malpartida, Humberto Miguel, Malta, Marília Brinati, de Sá Lima, Larrissa, Scavone, Cristóforo, Ferreira, Zulma S., Markus, Regina P., Marcourakis, Tania
• Format: Article
• Language: English
• Subjects: Aconitine - analogs & derivatives; Aconitine - pharmacology; Animals; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Inflammation - metabolism; Lipopolysaccharides - pharmacology; LPS; Male; Mecamylamine - pharmacology; NF-kappa B - metabolism; NF-κB; Nicotine; Nicotine - pharmacology; Nicotinic Agonists - pharmacology; Rats, Wistar; Receptors, Nicotinic - metabolism; Signal Transduction - drug effects; TLR-4; Toll-Like Receptor 4 - metabolism; α7 nicotinic acetylcholine receptors
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2016.10.056

•Chronic nicotine administration inhibited the nuclear binding of NF-κB.•Chronic nicotine inhibited the NF-κB-regulated mRNA expression of Tnf, Il1b, Nos2, and Tlr4.•Chronic treatment with methyllycaconitine and mecamylamine inhibited the effects of nicotine on the LPS-induced activation of NF-κB.•nAChRs are potential targets for modulating antiinflammatory responses in the brain. The hippocampus is a brain region that is rich in nicotinic acetylcholine receptors (nAChRs), especially the α7 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-κB (NF-κB) and the expression of LPS-induced inflammatory response genes. The results indicated that chronic nicotine administration (0.1mg/kg, s.c., 14days) inhibited the LPS-induced nuclear binding of NF-κB and mRNA expression levels of Tnf, Il1b, Nos2, and Tlr4. The presence of both the selective α7 nAChR antagonist methyllycaconitine (MLA; 5.0mg/kg i.p., 14days) and the nonselective nAChR antagonist mecamylamine (Meca; 1.0mg/kg, s.c., 14days) reversed the inhibitory effects of nicotine. These results suggest that the chronic activation of α7- and αxβy-containing nAChRs reduces acute inflammatory responses in the brain.