Decline of striatal dopamine release in parkin-deficient mice shown by ex vivo autoradiography
Decline of striatal dopamine release in parkin-deficient mice shown by ex vivo autoradiography
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DOI：
10.1002/jnr.21032
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发表时间：
2006-11-01
影响因子：
4.2
通讯作者：
Hattori, Nobutaka
中科院分区：
文献类型：
--
作者：
Sato, Shigeto;Chiba, Tomoki;Hattori, Nobutaka
Parkin基因是常染色体隐性遗传性青少年帕金森综合征（AR-JP）的致病基因。多巴胺（DA）代谢与帕金森病（PD）有关。为了了解AR-JP的发病机制，我们制备了parkin缺陷小鼠，以评估DA信号通路的状态，并通过离体放射自显影术检测DA释放和DA受体。使用[C-11]雷氯必利的离体放射自显影显示，帕金森病缺陷小鼠甲基苯丙胺激发后内源性DA释放明显减少。此外，帕金缺乏症与纹状体中DA（D-1和D-2）受体结合的显著上调和中脑中DA水平的增加有关。我们的研究结果表明，多巴胺能神经元在神经元死亡之前可能会表现出异常。(c)2006威利-利斯公司
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 [C-11]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. (c) 2006 Wiley-Liss, Inc.