Voltage-Gated Sodium Channels Are Involved in Cognitive Impairments in Parkinson's Disease- like Rats

Abstract

Cognitive impairment is one of the common non-motor symptoms in Parkinson's disease (PD). The hippocampus is a critical structure for learning and memory processes. The abnormal synaptic plasticity in the hippocampus is suggested to be associated with cognitive dysfunction in PD. Voltage gated sodium channels (VGSCs) are key molecules involved in synaptic transmission in the nervous system. Here, the expression patterns of VGSC subtypes Nav1.1, Nav1.3, Nav1.6 in the hippocampus of 6-hydroxydopamine (6-OHDA) lesioned rats were investigated at different time points after 6-OHDA injection. The results showed that the expression of Nav1.1 was remarkably increased in reactive astrocytes at 28days, whereas was sharply reduced at 49days after 6-OHDA injection. However, the expression of Nav1.6 was not different from the control hippocampus at 28days, but was abundantly increased in neurons of the contralateral and ipsilateral hippocampus at 49days after 6-OHDA injection. Moreover, Nav1.3, a subtype predominantly expressed at embryonic stage, was scatteredly re-expressed in neurons of the CA area in the contralateral and ipsilateral hippocampus at 49days after 6-OHDA injection. Furthermore, spatial learning and memory in 6-OHDA lesioned rats were effectively improved by acute treatment with a VGSCs blocker, phenytoin. These findings suggested that VGSCs may play an important role in the genesis of cognitive deficits in PD.