Astrocytes convert the parkinsonism inducing neurotoxin, MPTP, to its active metabolite, MPP+

Abstract

The ability of astrocytes to convert 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) to its toxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) was directly tested. Cultured astrocytes rapidly converted MPTP (25 micrograms/ml) to MPP+; after 6 h MPP+ concentrations reached 1.5 micrograms/ml, within the toxic range for neurons. MPTP (above 10 micrograms/ml) reduced glial density after 5 days of exposure. This toxic effect was blocked by pargyline, a monoamine oxidase inhibitor; pargyline also reduced the conversion of MPTP to MPP+ by 85%. When neurons were added to astrocyte cultures, MPTP conversion to MPP+ was not enhanced. Astrocytes appear critical in converting MPTP to MPP+, and are damaged by chronic exposure to MPTP.