title: The parkinsonian mimetic, MPP+, specifically impairs mitochondrial transport in dopamine axons.
abstract: Impaired axonal transport may play a key role in Parkinson's disease. To test this notion, a microchamber system was adapted to segregate axons from cell bodies using green fluorescent protein-labeled mouse dopamine (DA) neurons. Transport was examined in axons challenged with the DA neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP+). MPP+ rapidly reduced overall mitochondrial motility in DA axons; among motile mitochondria, anterograde transport was slower yet retrograde transport was increased. Transport effects were specific for DA mitochondria, which were smaller and transported more slowly than their non-DA counterparts. MPP+ did not affect synaptophysin-tagged vesicles or any other measureable moving particle. Toxin effects on DA mitochondria were not dependent upon ATP, calcium, free radical species, JNK, or caspase3/PKC pathways but were completely blocked by the thiol-anti-oxidant N-acetyl-cysteine or membrane-permeable glutathione. Since these drugs also rescued processes from degeneration, these findings emphasize the need to develop therapeutics aimed at axons as well as cell bodies to preserve "normal" circuitry and function as long as possible.
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
authors.forename: Jeong Sook
authors.initials: JS
authors.lastname: Kim-Han
authors.forename: Jo Ann
authors.initials: JA
authors.lastname: Antenor-Dorsey
authors.forename: Karen L
authors.initials: KL
authors.lastname: O'Malley
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D001370:Axonal Transport / Q000187:drug effects*; D001369:Axons / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*
chemical_list: D009498:Neurotoxins; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine