Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) in the mouse: relationships between monoamine oxidase, MPTP metabolism and neurotoxicity.
Mice treated with MPTP had a marked decrement in their neostriatal content of dopamine and its metabolites compared to controls and a severe loss of nerve cells in the zona compacta of the substantia nigra. Furthermore, neostriatal synaptosomal preparations from MPTP-treated mice had a greatly diminished capacity to take up 3H-dopamine compared to control. These biochemical and histological changes seen in MPTP-treated mice are similar to those observed in Parkinson patients. In mice treated with the specific MAO-B inhibitor deprenil prior to MPTP, these changes were not observed. It thus follows that deprenil is able to protect against the MPTP-induced dopaminergic neurotoxicity in mice. These data suggest a critical role for MAO-B in MPTP-induced neurotoxicity.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001596:Benzylamines / Q000378:metabolism; D003010:Clorgyline / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism*; D011725:Pyridines / Q000633:toxicity*; D012642:Selegiline / Q000494:pharmacology; D013378:Substantia Nigra / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D014363:Tryptamines / Q000378:metabolism
D001596:Benzylamines; D011725:Pyridines; D014363:Tryptamines; D015102:3,4-Dihydroxyphenylacetic Acid; D012642:Selegiline; C030820:tryptamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C030796:benzylamine; D008995:Monoamine Oxidase; D003010:Clorgyline; D004298:Dopamine; D006719:Homovanillic Acid