The biotransformation of MPTP and disposition of MPP+: the effects of aging.
The primary objective of this study was to investigate possible biochemical correlates of the enhanced effects of MPTP with aging in C57BL/6 mice. Striatal MPP+ concentrations were found to increase directly with the age of the animals injected (range 6 to 32 weeks). In vitro studies confirmed an enhanced rate of production of MPP+ in striatum, ventral mesencephalon, and frontal cortex in older animals. The rate of clearance of MPP+ from striatum was approximately the same in 6-8 week old mice as in 8 month old mice, but the total exposure of this brain region to MPP+ was approximately three times greater when older animals were compared to younger ones given equivalent doses of MPTP. These results are compatible with increased MPP+ production (i.e., a pharmacokinetic effect) as the explanation for the increased dopamine depletion induced by MPTP in older animals. We suggest that this approach may provide a new avenue of investigation for the study of neurodegenerative phenomena and the aging process.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D000375:Aging; D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D051379:Mice; D011725:Pyridines / Q000378:metabolism*; D011726:Pyridinium Compounds / Q000378:metabolism*
D011725:Pyridines; D011726:Pyridinium Compounds; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium