Muscarinic receptors prevent oxidative stress-mediated apoptosis induced by domoic acid in mouse cerebellar granule cells.

In mouse cerebellar granule neurons (CGNs) low concentrations of domoic acid (DomA) induce apoptotic cell death, which is mediated by oxidative stress; apoptosis is more pronounced in CGNs from Gclm (-/-) mice, which lack the modifier subunit of glutamate cysteine ligase (GCL) and have very low GSH levels. By activating M(3) muscarinic receptors, the cholinergic agonist carbachol inhibits DomA-induced apoptosis, and the anti-apoptotic action of carbachol is more pronounced in CGNs from Gclm (+/+) mice. Carbachol does not prevent DomA-induced increase in reactive oxygen species, suggesting that its anti-apoptotic effect is downstream of reactive oxygen species production.