EVOLUTION OF NERVE-FIBER DEGENERATION IN THE STRIATUM IN THE MPTP-TREATED SQUIRREL-MONKEY

We have examined the ultrastructure of the striatum in squirrel monkey s 1-5 d after a single sc injection of 1-methyl-4-phenyl-1,2,3,6-tetra hydropyridine (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 vacuo lation of the tissue, perhaps related to the striosome/matrix mosaic o f the neostriatum. The vacuolation involved not only terminals, but al so other parts of the neuropil. The severity of the destructive proces s 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 a ctive 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 administ ration. It is, however, possible that the time-course might differ bet ween the two locations with even shorter time intervals or changes in dosage of MPTP.