1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- induced damage of striatal dopaminergic fibers attenuates subsequent astrocyte response to MPTP

Abstract

Acute administration of the dopaminergic neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the C57BL/6 mouse caused a rapid decrease in the amount of striatal tyrosine hydroxylase (TH), a marker of the nigrostriatal dopaminergic pathway, followed by a large increase in the astrocyte protein, glial fibrillary acidic protein (GFAP). The astrocyte (GFAP) response declined to baseline three weeks after administration of MPTP. Administration of a second dosage of MPTP at this time evoked a second GFAP response. The magnitude of the second response, however, was decreased in comparison to the response seen after only a single exposure to MPTP. Increasing the initial dosage of MPTP resulted in greater reductions of the second GFAP response. These data indicate that MPTP-induced damage or loss of striatal dopaminergic neurons reduces the signal available for initiating astrogliosis and thereby reduces the astrocyte response to a second exposure to MPTP.