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Decline of striatal dopamine release in parkin‐deficient mice shown by ex vivo autoradiography
Author(s) -
Sato Shigeto,
Chiba Tomoki,
Nishiyama Shingo,
Kakiuchi Takeharu,
Tsukada Hideo,
Hatano Taku,
Fukuda Takahiro,
Yasoshima Yasunobu,
Kai Nobuyuki,
Kobayashi Kazuto,
Mizuno Yoshikuni,
Tanaka Keiji,
Hattori Nobutaka
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21032
Subject(s) - parkin , dopaminergic , dopamine , raclopride , ex vivo , striatum , dopamine receptor d2 , in vivo , methamphetamine , parkinson's disease , endocrinology , parkinsonism , biology , medicine , pharmacology , disease , genetics
Parkin is the causal gene of autosomal recessive juvenile parkinsonism (AR‐JP). Dopamine (DA) metabolism has been linked to Parkinson's disease (PD). To understand the pathogenesis of AR‐JP, we generated parkin‐deficient mice to assess the status of DA signaling pathway and examine DA release and DA receptor by ex vivo autoradiography. Ex vivo autoradiography using [ 11 C]raclopride showed a clear decrease in endogenous DA release after methamphetamine challenge in parkin‐deficient mice. Furthermore, parkin deficiency was associated with considerable upregulation of DA (D 1 and D 2 ) receptor binding in vivo in the striatum and increased DA levels in the midbrain. Our results suggest that dopaminergic neurons could behave abnormally before neuronal death. © 2006 Wiley‐Liss, Inc.