Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system
Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system
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DOI：
10.1016/s0896-6273(00)80886-7
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发表时间：
2000-01-01
期刊：
影响因子：
16.2
通讯作者：
Rosenthal, A
中科院分区：
文献类型：
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作者：
Abeliovich, A;Schmitz, Y;Rosenthal, A
α-突触核蛋白 (α-Syn) 是一种功能未知的 14 kDa 蛋白质，与帕金森病 (PD) 的病理生理学有关。在这里，我们证明 α-Syn(-/-) 小鼠具有存活能力和生育能力，表现出完整的大脑结构，并具有正常的多巴胺能细胞体、纤维和突触。 α-Syn(-/-) 小鼠的黑质纹状体末端表现出响应简单电刺激的标准多巴胺 (DA) 释放和再摄取模式。然而，它们在配对刺激下表现出增加的释放，可以通过升高的 Ca2+ 来模拟。与 DA 释放改变同时，α-Syn(-/-) 小鼠表现出纹状体 DA 减少和对安非他明的 DA 依赖性运动反应减弱。这些发现支持以下假设：α-Syn 是 DA 神经传递的重要突触前、活动依赖性负调节因子。
alpha-Synuclein (alpha-Syn) is a 14 kDa protein of unknown function that has been implicated in the pathophysiology of Parkinson's disease (PD). Here, we show that alpha-Syn(-/-) mice are viable and fertile, exhibit intact brain architecture, and possess a normal complement of dopaminergic cell bodies, fibers, and synapses. Nigrostriatal terminals of alpha-Syn(-/-) mice display a standard pattern of dopamine (DA) discharge and reuptake in response to simple electrical stimulation. However, they exhibit an increased release with paired stimuli that can be mimicked by elevated Ca2+. Concurrent with the altered DA release, alpha-Syn(-/-) mice display a reduction in striatal DA and an attenuation of DA-dependent locomotor response to amphetamine. These findings support the hypothesis that alpha-Syn is an essential presynaptic, activity-dependent negative regulator of DA neurotransmission.