Acute and chronic effects of aluminum on acetyl-CoA and acetylcholine metabolism in differentiated and nondifferentiated SN56 cholinergic cells.

Mechanisms of preferential loss of cholinergic neurons in the course of neurodegenerative diseases are unknown. Therefore, we investigated whether differentiation-evoked changes in acetyl-CoA and acetylcholine metabolism contribute to the susceptibility of cholinergic neuroblastoma to cytotoxic effects of Al. In SN56 cells differentiated with retinoic acid and dibutyryl cAMP (DC), pyruvate utilization and acetyl-CoA content were lower and acetylcholine level higher than in nondifferentiated cells (NC), respectively. In DC Al and Ca accumulations were 50% and 100%, respectively higher than in NC. Acute Al addition caused inhibition, whereas its chronic application had no effect on pyruvate utilization both in NC and in DC. On the other hand, in both experiments, Al evoked a greater decrease of acetyl-CoA level in DC than in NC. Acute addition of Al depressed acetylcholine release from DC to two times lower values than in NC. On the other hand, chronic addition of Al increased ACh release from DC over twofold, being without effect on its release from NC. These findings indicate that higher accumulation of Ca, along with low levels of acetyl-CoA, could make DC more susceptible to neurotoxic inputs than NC. Excessive acetylcholine release, evoked by Al, is likely to increase acetyl-CoA utilization for resynthesis of the neurotransmitter pool and cause deficit of this metabolite in DC. On the other hand, NC, owing to lower Ca accumulation, slower ACh metabolism, and higher level of acetyl-CoA, would be less prone to these harmful conditions. Copyright 2000 Wiley-Liss, Inc.