Decline of striatal dopamine release in parkin-deficient mice shown by ex vivo autoradiography
✍ Scribed by Shigeto Sato; Tomoki Chiba; Shingo Nishiyama; Takeharu Kakiuchi; Hideo Tsukada; Taku Hatano; Takahiro Fukuda; Yasunobu Yasoshima; Nobuyuki Kai; Kazuto Kobayashi; Yoshikuni Mizuno; Keiji Tanaka; Nobutaka Hattori
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 738 KB
- Volume
- 84
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
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.