Acetyl-CoA metabolism in cholinergic neurons and their susceptibility to neurotoxic inputs

Cholinergic neurons, unlike other brain cells utilize acetyl-CoA not only f or energy production but also for acetylcholine (ACh) synthesis. Therefore, suppression of acetyl-CoA metabolism by different neurotoxic inputs may be particularly harmful for this group of cells. Differentiation of SN56 chol inergic hybrid cells increased their choline acetyltransferase (ChAT) activ ity and ACh content but depressed pyruvate dehydrogenase activity and acety l-CoA content. Differentiated cells were more susceptible to acute and chro nic influences of aluminum, NO and amyloid-P. Al decreased acetyl-CoA conte nt, ACh release and increased Ca accumulation in differentiated cells (DC) to much higher degree than in non-differentiated ones(NC). NO strongly depr essed acetyl-CoA level and increased ACh release in DC but did not affect N C. Additive effects of Al and NO were seen in DC but not in NC. Also long t erm suppressory effects of amyloid-P, Al and NO on cholinergic phenotype an d morphologic maturation were more evident in DC than in NC. Thus, relative shortage of acetyl-CoA in highly differentiated cholinergic neurons could make them particularly susceptible to degenerative insults in the course of different cholinergic encephalopathies.