Effect of cholinergic signaling on neuronal cell bioenergetics. J Alzheimers Dis 2013;33(4):1135-46
Date
10/27/2012Pubmed ID
23099815Pubmed Central ID
PMC3553319DOI
10.3233/JAD-2012-121822Scopus ID
2-s2.0-84873641621 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
Alzheimer's disease (AD) patients have reduced brain acetylcholine and reversing this deficit yields clinical benefits. In this study we explored how increased cholinergic tone impacts cell bioenergetics, which are also perturbed in AD. We treated SH-SY5Y neuroblastoma cells with carbachol, a cholinergic agonist, and tested for bioenergetic flux and bioenergetic infrastructure changes. Carbachol rapidly increased both oxidative phosphorylation and glycolysis fluxes. ATP levels rose slightly, as did cell energy demand, and AMPK phosphorylation occurred. At least some of these effects depended on muscarinic receptor activation, ER calcium release, and ER calcium re-uptake. Our data show that increasing cholinergic signaling enhances cell bioenergetics, and reveal mechanisms that mediate this effect. Phenomena we observed could potentially explain why cholinesterase inhibitor therapy increases AD brain glucose utilization and N-acetyl aspartate levels. The question of whether cholinesterase inhibitors have a disease modifying effect in AD has long been debated; our data suggest a theoretical mechanism through which such an effect could potentially arise.
Author List
Lu J, E L, Roy N, Hutfles L, Selfridge E, Funk E, Burns JM, Swerdlow RHAuthor
Lezi E PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AcetylcholineCarbachol
Cell Line, Tumor
Cholinergic Agonists
Energy Metabolism
Glycolysis
Humans
Neuroblastoma
Neurons
Signal Transduction
