Mice Lacking α-Synuclein Display Functional Deficits in the Nigrostriatal Dopamine System
摘要：
α-Synuclein (α-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 α-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 α-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 Ca 2+. Concurrent with the altered DA release, α-Syn −/− mice display a reduction in striatal DA and an attenuation of DA-dependent locomotor response to amphetamine. These findings support the hypothesis that α-Syn is an essential presynaptic, activity-dependent negative regulator of DA neurotransmission.
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关键词：
Corpus Striatum Dopamine Nerve Tissue Proteins Substantia Nigra rab3A GTP Binding Protein 纹状体 多巴胺 神经组织蛋白质类 黑质
DOI：
10.1016/S0896-6273(00)80886-7
被引量：
年份：
2000
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