GM-1 GANGLIOSIDE PROMOTES THE RECOVERY OF SURVIVING MIDBRAIN DOPAMINERGIC-NEURONS IN MPTP-TREATED MONKEYS

We have examined the influence of chronic GM-1 treatment (20 mg/kg i.m . for 16 consecutive days) on the extent of dopaminergic damage induce d by acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) adminis tration in cynomolgus monkeys using immunohistochemical and neurochemi cal analysis. The total number of tyrosine hydroxylase-immunoreactive neurons was reduced in different catecholaminergic mesencephalic regio ns of MPTP-treated monkeys such as substantia nigra pars compacta, mai nly in the ventral portion of the nucleus (39% reduction), substantia nigra pars lateralis (31%), peri- and retrorubral catecholaminergic ce ll group and ventral tegmental area (A8 and A10 respectively, 20% redu ction). A similar degree of neuronal loss was observed in the MPTP + G M-1-treated animals, suggesting that GM-1 ganglioside does not exert a protective effect against MPTP-induced dopaminergic cell loss. Moreov er, no neurochemical recovery from the striatal dopaminergic depletion induced by MPTP was found after GM-1 treatment. However, the optical density of tyrosine hydroxylase fibers and the cellular tyrosine hydro xylase content were increased in the substantia nigra pars compacta an d ventral tegmental area of the MPTP-treated monkeys which received GM -1 ganglioside, compared with animals treated only with the neurotoxin . These results indicate that GM-1 does not protect against cell death but exerts a neurotrophic effect on surviving dopaminergic neurons in the midbrain of MPTP-lesioned monkeys, suggesting that GM-1 gangliosi de may be potentially useful for the treatment of neurodegenerative di sorders such as Parkinson's disease.