G(M1) GANGLIOSIDE RESCUES SUBSTANTIA-NIGRA PARS COMPACTA NEURONS AND INCREASES DOPAMINE SYNTHESIS IN RESIDUAL NIGROSTRIATAL DOPAMINERGIC-NEURONS IN MPTP-TREATED MICE

G(M1) 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 G(M1) 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 + G(M1)-treated mice than in mice that received only MPTP, This effect of G(M1) on dopamine synthesis was dependent upon the degree of initial damage to the nigrostriatal dopamine system, That is, the G(M1) 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 G(M1) on rescue and repair of dopaminergic neurons, G(M1) may also have the ability to enhance dopamine synthesis in residual dopaminergic neurons, Direct effects on dopamine neurochemistry may contribute to functional improvements seen after G(M1) treatment in various models of parkinsonism. (C) 1995 Wiley Liss, Inc.