Effects of GM1 ganglioside treatment on pre- and postsynaptic dopaminergicmarkers in the striatum of parkinsonian monkeys

GM1 ganglioside administration has previously been shown to increase striat al dopamine levels and to enhance the density of tyrosine hydroxylase-posit ive fibers in the striatum of monkeys made parkinsonian by 1-methyl-4-pheny l-1,2,3,6-tetrahydropyridine (MPTP). The present study examined the extent to which GM1 administration promotes recovery of dopamine terminals and rev erses lesion-induced changes in postsynaptic receptors in the striatum of M PTP-treated monkeys. All MPTP-treated animals developed severe parkinsonism . GM1-treated monkeys exhibited significant functional recovery after 6 wee ks of treatment, whereas saline-treated controls remained parkinsonian over the same time period. MPTP exposure resulted in profound decreases in [H-3 ]-mazindol binding to dopamine transporters in the caudate and putamen and increased D1 and D2 receptor binding in several striatal regions. GM1 treat ment resulted in significant increases in striatal [H-3]-mazindol binding a nd decreases in D1 binding compared to control animals in many striatal reg ions. GM1 treatment did not significantly affect D2 binding. These results show that GM1 treatment can partially restore striatal dopaminergic termina ls and partially reverse postsynaptic changes in dopamine receptors in a no nhuman primate model of parkinsonism. (C) 2000 Wiley-Liss, Inc.