GM1 ganglioside rescues substantia nigra pars compacta neurons and increases dopamine synthesis in residual nigrostriatal dopaminergic neurons in MPTP-treated mice.
GM1 ganglioside has been shown to stimulate recovery of the damaged dopamine system under a number of different circumstances. In addition to rescue of damaged dopamine neurons, the present study assessed the ability of GM1 to enhance the synthesis of dopamine in remaining nigrostriatal neurons following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure. There was a significantly greater accumulation of L-dopa 30 min after aromatic amino acid decarboxylase inhibition with NSD-1015 (100 mg/kg) and an increase in the ratio of L-dopa to dopamine in MPTP+GM1-treated mice than in mice that received only MPTP. This effect of GM1 on dopamine synthesis was dependent upon the degree of initial damage to the nigrostriatal dopamine system. That is, the GM1 effect on dopamine synthesis could not be demonstrated in mice with greater than 95% striatal dopamine loss and 75% substantia nigra dopamine neuron loss. These results suggest that in addition to previously reported effects of GM1 on rescue and repair of dopaminergic neurons, GM1 may also have the ability to enhance dopamine synthesis in residual dopaminergic neurons. Direct effects on dopamine neurochemistry may contribute to functional improvement seen after GM1 treatment in various models of parkinsonism.
Schneider
J S
JS
Center for Neurological Research of the Department of Neurology, Hahnemann University, Philadelphia, Pennsylvania 19102, USA.
Kean
A
A
DiStefano
L
L
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D007980:Levodopa / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects; D010300:Parkinson Disease; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism
D005677:G(M1) Ganglioside; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine