Evolution of nerve fiber degeneration in the striatum in the MPTP-treated squirrel monkey.

We have examined the ultrastructure of the striatum in squirrel monkeys 1-5 d after a single sc injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 2.5 mg/kg. One untreated monkey served as control. We expected to find a dense degeneration of the dopamine terminals, but found instead that the main abnormality consisted of a focal vacuolation of the tissue, perhaps related to the striosome/matrix mosaic of the neostriatum. The vacuolation involved not only terminals, but also other parts of the neuropil. The severity of the destructive process increased from d 1-5. We conclude that MPP+, the toxic metabolite of MPTP, may gain access to the neuropil, either before or after its active uptake into and subsequent destruction of the dopamine terminals. In the present study, abnormalities were observed simultaneously in the striatum and substantia nigra as early as 24 h after MPTP administration. It is, however, possible that the time-course might differ between the two locations with even shorter time intervals or changes in dosage of MPTP.