[Recovery of nigrostriatal and mesolimbic dopaminergic system following administration of ganglioside in MPTP-treated mice]

Abstract

The effects of systemic injection of GM 1 ganglioside on dopaminergic (DA) nigrostriatal and mesolimbic system following 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP) have been studied in C 57 BL/6 mice. MPTP treatment (4 x 20 mg/kg i.p. given 12 hr apart) resulted in significant depletion of DA concentration in the major terminal fields of the nigrostriatal and mesolimbic DA systems, i.e. dorsal striatum, ventral striatum, nucleus accumbens and olfactory tubercle 5 weeks after treatment in young (2 month old) mice. In aging (12 month old) mice treated with MPTP, significant depletion of DA concentration was observed in the cell body regions, i.e. substantia nigra and ventral tegmental area in addition to the major terminal fields, suggesting that the effect of MPTP is more widespread in aging mice. Although GM 1 ganglioside treatment (30 mg/kg, i.p. daily for 5 weeks) partially restored DA concentration in every major terminal field in young mice, such an apparent recovery was not seen in aging mice. GM 1 ganglioside treatment also reduced the increased 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratio following MPTP injection in the striatum of young mice, but such an effect was not observed in aging mice. We conclude that DA nigrostriatal and mesolimbic system in aging mice demonstrates reduced regenerative capacity following MPTP depletion compared with young mice, and the beneficial effect of GM 1 ganglioside for the recovery of DA nigrostriatal and mesolimbic system neurons declines with age.