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 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.
Herrero
M T
MT
INSERM U289, Hôpital de la Salpêtrière, Paris, France.
Perez-Otaño
I
I
Oset
C
C
Kastner
A
A
Hirsch
E C
EC
Agid
Y
Y
Luquin
M R
MR
Obeso
J A
JA
Del Rio
J
J
D000818:Animals; D015415:Biomarkers; D016923:Cell Death / Q000187:drug effects; D004298:Dopamine; D005677:G(M1) Ganglioside / Q000494:pharmacology / Q000627:therapeutic use*; D020267:MPTP Poisoning; D008252:Macaca fascicularis; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D015415:Biomarkers; D009419:Nerve Tissue Proteins; D005677:G(M1) Ganglioside; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine