CHRONIC MPTP TREATMENT REPRODUCES IN BABOONS THE DIFFERENTIAL VULNERABILITY OF MESENCEPHALIC DOPAMINERGIC-NEURONS OBSERVED IN PARKINSONS-DISEASE

Chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to baboons was shown previously to result in a motor syndrome and a pattern of striatal dopaminergic fibre loss similar to those obs erved in idiopathic Parkinson's disease. In the present study, tyrosin e hydroxylase-immunoreactive neurons were quantified in the mesencepha lon of control (n = 4) and chronically MPTP-treated (n = 3) baboons. M PTP induced a significant reduction in neuronal cell density in the su bstantia nigra (63.8% reduction) and the ventral tegmental area (53.1% ). Within the substantia nigra, obvious mediolateral and dorsoventral gradients of neuronal cell loss were observed. First, the pars lateral is was more affected than the lateral divisions of the pars compacta ( 89.6% vs 73.8% cell loss), which in turn were more depleted than the m edial divisions (60.1% reduction). Second, the ventral regions of the pars compacta were more degenerated than the dorsal parts (82.4 vs 51. 5% decrease). This regional pattern is strikingly similar to that obse rved in Parkinson's disease and indicates that two subpopulations of d opaminergic neurons are distinguishable on the basis of their differen tial vulnerability to MPTP. Finally, the present study confirms that c hronic mitochondrial complex I inhibition using MPTP in primates is su fficient to reproduce the typical dopaminergic cell loss and striatal fibre depletion observed in Parkinson's disease.