title: Minocycline enhances MPTP toxicity to dopaminergic neurons.
abstract: Minocycline has been shown previously to have beneficial effects against ischemia in rats as well as neuroprotective properties against excitotoxic damage in vitro, nigral cell loss via 6-hydroxydopamine, and to prolong the life-span of transgenic mouse models of Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). We investigated whether minocycline would protect against toxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin that selectively destroys nigrostriatal dopaminergic (DA) neurons and produces a clinical state similar to Parkinson's disease (PD) in rodents and primates. We found that although minocycline inhibited microglial activation, it significantly exacerbated MPTP-induced damage to DA neurons. We present evidence suggesting that this effect may be due to inhibition of DA and 1-methyl-4-phenylpridium (MPP+) uptake into striatal vesicles.
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005911:Gliosis / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D008911:Minocycline / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D013752:Tetracycline / Q000494:pharmacology
chemical_list: D018696:Neuroprotective Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D013752:Tetracycline; D008911:Minocycline; D004318:Doxycycline; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine