GM-1 ganglioside promotes the recovery of surviving midbrain dopaminergic neurons in MPTP-treated monkeys
Herrero MT, Perez-Otaño I, Oset C, Kastner A, Hirsch EC, Agid Y, Luquin MR, Obeso JA, Del Rio J.
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 induced by acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in cynomolgus monkeys using immunohistochemical and neurochemical analysis.
The total number of tyrosine hydroxylase-immunoreactive neurons was reduced in different catecholaminergic mesencephalic regions of MPTP-treated monkeys such as substantia nigra pars compacta, mainly in the ventral portion of the nucleus (39% reduction), substantia nigra pars lateralis (31%), peri- and retrorubral catecholaminergic cell group and ventral tegmental area (A8 and A10 respectively, 20% reduction). A similar degree of neuronal loss was observed in the MPTP+GM-1-treated animals, suggesting that GM-1 ganglioside does not exert a protective effect against MPTP-induced dopaminergic cell loss. Moreover, 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 hydroxylase content were increased in the substantia nigra pars compacta and 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 ganglioside may be potentially useful for the treatment of neurodegenerative disorders such as Parkinson's disease.
CITA DEL ARTÍCULO Neuroscience. 1993 Oct;56(4):965-72