Medicine and Health Sciences Commons^™

Forebrain Cholinergic Signaling Regulates Innate Immune Responses And Inflammation, Ashbeel Roy, Vania F. Prado, Marco A.M Prado, Robert Gros, Kurt R. Lehner, Harold A. Silvernman, Meghan E. Addorissio, Mohammed A. Al-Onaizi, Yaakov Levine, Peder S. Olofsson, Sangeeta S. Chavan, Neil M. Nathanson, Yousef Al-Abed, Christine N. Metz, Kevin J. Tracey, Valentin A. Pavlov

Anatomy and Cell Biology Publications

The brain regulates physiological functions integral to survival. However, the insight into brain neuronal regulation of peripheral immune function and the neuromediator systems and pathways involved remains limited. Here, utilizing selective genetic and pharmacological approaches, we studied the role of forebrain cholinergic signaling in the regulation of peripheral immune function and inflammation. Forebrain-selective genetic ablation of acetylcholine release and vagotomy abolished the suppression of serum TNF by the centrally-acting cholinergic drug galantamine in murine endotoxemia. Selective stimulation of acetylcholine action on the M1 muscarinic acetylcholine receptor (M1 mAChR) by central administration of the positive allosteric modulator benzyl quinolone carboxylic acid …