Inhibitory role of cholinergic system mediated via alpha7 nicotinic acetylcholine receptor in LPS-induced neuro-inflammation.

Abstract

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 microg) was used to induce neuro-inflammation in rats and estimations of pro-inflammatory cytokines, alpha7 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 alpha7 nAChR antagonist or dihydro-beta-erythroidine (DHbetaE; 1.25, 2.5 and 5 mg/kg, i.p.), an alpha4beta2 nAChR antagonist, was given 20 min prior to nicotine in LPS-treated rats. Methyllycaconitine antagonized the anti-inflammatory effect of nicotine whereas DHbetaE showed no effect demonstrating that alpha7 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 alpha7 nicotinic acetylcholine receptor and muscarinic receptors are not involved.

• Authors: Ethika Tyagi, Rahul Agrawal, Chandishwar Nath, Rakesh Shukla
• Journal: Innate immunity (Innate Immun) Vol. 16 Issue 1 Pg. 3-13 (Feb 2010) ISSN: 1753-4267 [Electronic] United States
• PMID: 19586999 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chrna7 protein, rat
• Cytokines
• Inflammation Mediators
• Lipopolysaccharides
• Nicotinic Agonists
• Nicotinic Antagonists
• Receptors, Nicotinic
• alpha7 Nicotinic Acetylcholine Receptor
• nicotinic receptor alpha4beta2
• methyllycaconitine
• Dihydro-beta-Erythroidine
• Oxotremorine
• Nicotine
• Aconitine

Topics

• Aconitine (administration & dosage, analogs & derivatives)
• Animals
• Brain (drug effects, immunology, metabolism)
• Cytokines (genetics, immunology, metabolism)
• Dihydro-beta-Erythroidine (administration & dosage)
• Encephalitis (chemically induced, immunology)
• Gene Expression Regulation (drug effects, immunology)
• Inflammation Mediators (immunology, metabolism)
• Lipopolysaccharides (administration & dosage)
• Neuroimmunomodulation
• Nicotine (administration & dosage)
• Nicotinic Agonists (administration & dosage)
• Nicotinic Antagonists (administration & dosage)
• Oxotremorine (administration & dosage)
• Rats
• Rats, Sprague-Dawley
• Receptors, Nicotinic (immunology, metabolism)
• alpha7 Nicotinic Acetylcholine Receptor