title: Impaired in vivo dopamine release in parkin knockout mice.
abstract: parkin is the most frequent causative gene among familial Parkinson's disease (PD). Although parkin deficiency induces autosomal recessive juvenile parkinsonism (AR-JP, PARK2) in humans, parkin knockout (PKO) mice consistently show few signs of dopaminergic degeneration. We aimed to directly measure evoked extracellular dopamine (DA) overflow in the striatum with in vivo voltammetry. The amplitude of evoked DA overflow was low in PKO mice. The half-life time of evoked DA overflow was long in PKO mice suggesting lower release and uptake of dopamine. Facilitation of DA overflow by repetitive stimulation enhanced in the older PKO mice. Decreased dopamine release and uptake in young PKO mice suggest early pre-symptomatic changes in dopamine neurotransmission, while the enhanced facilitation in the older PKO mice may reflect a compensatory adaptation in dopamine function during the late pre-symptomatic phase of Parkinson's disease. Our results showed parkin deficiency may affect DA release in PKO mice, although it does not cause massive nigral degeneration or parkinsonian symptoms as in humans.
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: Genko
authors.initials: G
authors.lastname: Oyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshimi
authors.forename: Shihoko
authors.initials: S
authors.lastname: Natori
authors.forename: Yoko
authors.initials: Y
authors.lastname: Chikaoka
authors.forename: Yong-Ri
authors.initials: YR
authors.lastname: Ren
authors.forename: Manabu
authors.initials: M
authors.lastname: Funayama
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shimo
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.forename: Taizo
authors.initials: T
authors.lastname: Nakazato
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kitazawa
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging / Q000502:physiology; D000818:Animals; D001835:Body Weight; D003342:Corpus Striatum / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009627:Nomifensine / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency*
chemical_list: D015102:3,4-Dihydroxyphenylacetic Acid; D009627:Nomifensine; D006897:Hydroxyindoleacetic Acid; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D004298:Dopamine; D006719:Homovanillic Acid