Acute ultrastructural effects of MPTP on the nigrostriatal pathway of the C57BL/6 adult mouse: Evidence of compensatory plasticity in nigrostriatal neurons

Acute doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) elicited degenerative and apparently compensatory changes in the nigrostriatum of injected animals within 1 day of treatment. In the substantia nigra pars compacta (SNc), low-dose (20 mg/kg) administration elicited early degeneration of mitochondria in the absence of other effects. In the striatum, a low MPTP dose resulted in myelin unwinding, demyelination, cytoplasmic shrinkage, and disturbance of synaptic communication, as evinced by a profound reduction in synaptic vesicle production. High-dose (40 mg/kg) administration generated more drastic axonal degeneration leading to cell elimination in the striatum. At neither dose was mitochondrial disturbance evident in the striatum. Evidence is presented that darkened synaptic boutons, visible at this level of MPTP administration, were part of healthy enlarged axons with an elevated number of synaptic contacts. These spared neuronal processes, therefore, were hypothesized to compensate for the MPTP-induced death of dopaminergic neurons by adaptive structural modifications that would serve to enhance their functional capability. J. Neurosci. Res. 59:126–135, 2000 © 2000 Wiley-Liss, Inc.