Altered expression of voltage gated sodium channel Nav1.1 is involved in motor ability in MPTP-treated mice

电压门控钠通道 Nav1.1 的表达改变与 MPTP 治疗小鼠的运动能力有关

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作者:Weitang Liu, Wenwen Lao, Renxing Zhang, Hongyan Zhu

Abstract

Parkinson's disease (PD) is a motor disabling disorder owing to the progressive degeneration of dopaminergic neurons in the substantia nigra (SN). The mechanisms causing motor deficits remain debated. High synchronized oscillations in the basal ganglia (BG) were proposed to be associated with motor symptoms in PD patients and animal models of PD. Voltage-gated sodium channels play a vital role in the initiation and propagation of action potentials. Here, we investigated the expression patterns of a VGSC subtype Nav1.1 in the BG of a PD animal model induced by MPTP intraperitoneal injection. The results showed that Nav1.1 was significantly reduced in tyrosine hydroxylase (TH) positive dopaminergic neurons of the SN. Moreover, Nav1.1 expression was significantly increased in calcium binding protein parvalbumin (PV) positive neurons of the globus pallidus (GP) in MPTP-treated mice compared to the rarely undetectable expression of Nav1.1 in the control GP. Furthermore, the administration of phenytoin, a VGSCs blocker, can effectively improve motor disabilities and reduce the synchronous oscillations in the BG of MPTP-treated mice. These findings suggested that the alterations of Nav1.1 expression may be associated with the high synchronous oscillations in the BG of PD animals.

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