Inclusion dynamics in PC12 is comparable between amphetamines and MPTP

In previous studies it was demonstrated that amphetamine derivatives and 1-methyl article-4-phenylpyridinium produce neuronal cell bodies. In the present work, we compared the fine ultrastructure of the intracellular inclusions induced by these different neurotoxic treatments. In particular, we compared the dynamical changes occurring when a mild toxic stimulus acts for different time intervals. For this purpose, we exposed catecholamine-synthesizing PC12 cells to different amphetamine derivatives (methamphetamine and 3,4-methylenedioxymethamphetamine), or 1-methyl-4-phenylpyridinium ion, which represents the active metabolite of the neurotoxin 1-methyl-4-phenyl-1,3,4,6-tetrahydropyridine. Despite inclusions that are elicited by different mechanisms depending on the specific neurotoxin, their ultrastructural features are similar and there is a high parallelism in their temporal evolution. This suggests that formation of inclusions is a multi-step process that might be elicited by different stimuli and, once triggered, leads to the same final effect.