Astrocytes convert the parkinsonism inducing neurotoxin, MPTP, to its active metabolite, MPP+.
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.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D051379:Mice; D010293:Pargyline / Q000494:pharmacology; D011725:Pyridines / Q000378:metabolism*; D011726:Pyridinium Compounds / Q000378:metabolism*
D011725:Pyridines; D011726:Pyridinium Compounds; D010293:Pargyline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium