Impaired in vivo dopamine release in parkin knockout mice.
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.
Oyama
Genko
G
Department of Neurology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
Yoshimi
Kenji
K
Natori
Shihoko
S
Chikaoka
Yoko
Y
Ren
Yong-Ri
YR
Funayama
Manabu
M
Shimo
Yasushi
Y
Takahashi
Ryosuke
R
Nakazato
Taizo
T
Kitazawa
Shigeru
S
Hattori
Nobutaka
N
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*
D015102:3,4-Dihydroxyphenylacetic Acid; D009627:Nomifensine; D006897:Hydroxyindoleacetic Acid; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D004298:Dopamine; D006719:Homovanillic Acid