Inhibitory role of cholinergic system mediated via alpha7 nicotinic acetylcholine receptor in LPS-induced neuro-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 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.
Tyagi
Ethika
E
Division of Pharmacology, Central Drug Research Institute, Lucknow, India.
Agrawal
Rahul
R
Nath
Chandishwar
C
Shukla
Rakesh
R
D000157:Aconitine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004079:Dihydro-beta-Erythroidine / Q000008:administration & dosage; D004660:Encephalitis / Q000139:chemically induced / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D015213:Neuroimmunomodulation; D009538:Nicotine / Q000008:administration & dosage; D018722:Nicotinic Agonists / Q000008:administration & dosage; D018733:Nicotinic Antagonists / Q000008:administration & dosage; D010095:Oxotremorine / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000276:immunology / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579165:Chrna7 protein, rat; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D010095:Oxotremorine; D009538:Nicotine; D000157:Aconitine