Electron microscopic evidence for neurotoxicity in the basal ganglia

The dopaminergic projection from the substantia nigra to the neostriatum is vulnerable to several neurotoxins including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), amphetamine, and 5-hydroxydopamine. We have treated rats or mice with these agents and examined various regions of their brains with a combination of Fink-Heimer, immunohistochemical, serial-section electron microscopic, and three-dimensional reconstruction methods. In addition to degenerating or swollen axons, we found darkened glial processes and some damage to postsynaptic cells and dendrites. The particular effects observed critically depend on experimental variables such as dose, time, species and strain and raise questions about the correlation of light and electron microscopic results. These studies provide the basis for a discussion of the advantages and disadvantages of an ultrastructural examination of the effects of neurotoxins.