Fate of nigrostriatal neurons in young mature mice given 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A neurochemical and morphological reassessment

Abstract

The effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on nigrostriatal dopaminergic neurons in the mouse was re-examined in view of recent conflicting reports regarding the neurotoxic effect of MPTP in this experimental animal. It was found that while MPTP destroyed a substantial number of dopaminergic nerve terminals in the striatum of young mature (6-8 weeks old) mice, it left the majority of cells in the pars compacta of the substantia nigra (SNc) unaffected. It was also found that 5 months after MPTP treatment there was substantial, although incomplete, recovery of striatal DA nerve terminal markers (DA level, metabolites, uptake, [3H]mazindol binding). Given these observations, it is concluded that while the young mature MPTP mouse may not be a valid animal model of Parkinson's disease (since it does not develop severe SNc cell loss characteristic of this disorder), it will be valuable for the study of how MPTP destroys dopaminergic nerve terminals and may prove useful as an experimental system for studying recovery of dopaminergic fibers after injury and for exploring ways to accelerate this recovery.