Open AccessInhibitory role of cholinergic system mediated via α7 nicotinic acetylcholine receptor in LPS-induced neuro-inflammation
Author(s) -
Ethika Tyagi,
Rahul Agrawal,
Chandishwar Nath,
Rakesh Shukla
Publication year - 2009
Publication title -
innate immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.921
H-Index - 69
eISSN - 1753-4267
pISSN - 1753-4259
DOI - 10.1177/1753425909104680
Subject(s) - methyllycaconitine , oxotremorine , nicotine , muscarinic acetylcholine receptor , nicotinic antagonist , chemistry , acetylcholine , nicotinic agonist , endocrinology , pharmacology , cholinergic , proinflammatory cytokine , medicine , agonist , nicotinic acetylcholine receptor , receptor , inflammation
This study investigated the influence of the cholinergic system on neuro-inflammation using nicotinic and muscarinic receptor agonists and antagonists. Intracerebroventricular (ICV) injection of lipopolysaccharide (LPS, 50 µg) was used to induce neuro-inflammation in rats and estimations of pro-inflammatory cytokines, α7 nicotinic acetylcholine receptor (nAChR) mRNA expression were done in striatum, cerebral cortex, hippocampus and hypothalamus at 24 h after LPS injection. Nicotine (0.2, 0.4 and 0.8 mg/kg, i.p.) or oxotremorine (0.2, 0.4 and 0.8 mg/kg, i.p.) were administered 2 h prior to sacrifice. We found that only nicotine was able to block the proinflammatory cytokines induced by LPS whereas, oxotremorine was found ineffective. Methyllycaconitine (MLA; 1.25, 2.5 and 5 mg/kg, i.p.), an α7 nAChR antagonist or dihydro-β-erythroidine (DHβE; 1.25, 2.5 and 5 mg/kg, i.p.), an α4β2 nAChR antagonist, was given 20 min prior to nicotine in LPS-treated rats. Methyllycaconitine antagonized the anti-inflammatory effect of nicotine whereas DHβE showed no effect demonstrating that α7 nAChR is responsible for attenuation of LPS-induced pro-inflammatory cytokines. This study suggests that the inhibitory role of the central cholinergic system on neuro-inflammation is mediated via α7 nicotinic acetylcholine receptor and muscarinic receptors are not involved.