缺乏α-突触核蛋白的小鼠在黑质纹状体多巴胺系统中表现出功能缺陷。

Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system.

作者信息

Abeliovich A, Schmitz Y, Fariñas I, Choi-Lundberg D, Ho W H, Castillo P E, Shinsky N, Verdugo J M, Armanini M, Ryan A, Hynes M, Phillips H, Sulzer D, Rosenthal A

机构信息

Department of Neurology, University of California, San Francisco 94143, USA.

出版信息

Neuron. 2000 Jan;25(1):239-52. doi: 10.1016/s0896-6273(00)80886-7.

DOI:10.1016/s0896-6273(00)80886-7

PMID:10707987

Abstract

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.

摘要

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。在此，我们表明α-Syn基因敲除小鼠能够存活且可育，脑结构完整，多巴胺能细胞体、纤维和突触的数量正常。α-Syn基因敲除小鼠的黑质纹状体终末在受到简单电刺激时，表现出标准的多巴胺（DA）释放和再摄取模式。然而，它们在成对刺激下释放增加，这可被细胞外Ca2+升高所模拟。与DA释放改变同时发生的是，α-Syn基因敲除小鼠纹状体DA减少，对苯丙胺的DA依赖性运动反应减弱。这些发现支持了α-Syn是DA神经传递中一种重要的突触前、活动依赖性负调节因子的假说。