title: Chronic nicotine treatment decreases LPS signaling through NF-κB and TLR-4 modulation in the hippocampus.
abstract: 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.
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil; School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Cecília Cerqueira
authors.initials: CC
authors.lastname: Café-Mendes
authors.affiliation: School of Arts, Sciences and Humanities, University of São Paulo, São Paulo, Brazil.
authors.forename: Humberto Miguel
authors.initials: HM
authors.lastname: Garay-Malpartida
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Marília Brinati
authors.initials: MB
authors.lastname: Malta
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Larrissa
authors.initials: L
authors.lastname: de Sá Lima
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Cristóforo
authors.initials: C
authors.lastname: Scavone
authors.affiliation: Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Zulma S
authors.initials: ZS
authors.lastname: Ferreira
authors.affiliation: Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Regina P
authors.initials: RP
authors.lastname: Markus
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: tmarcour@usp.br.
authors.forename: Tania
authors.initials: T
authors.lastname: Marcourakis
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; C054634:methyllycaconitine; D008464:Mecamylamine; D009538:Nicotine; D000157:Aconitine
keywords: Hippocampus; LPS; NF-κB; Nicotine; TLR-4; α7 nicotinic acetylcholine receptors