Increased expression of Nav1.6 of reactive astrocytes in the globus pallidus is closely associated with motor deficits in a model of Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease in elderly people, which is characterized by motor disabilities in PD patients. Nav1.6 is the most abundant subtype of voltage-gated sodium channels (VGSCs) in the brain of adult mammals and rodents. Here we investigated the role of Nav1.6 in the external globus pallidus (GP) involved in the pathogenesis of motor deficits in unilateral 6-OHDA(6-hydroxydopamine)lesioned rats. The results show that Nav1.6 is dramatically increased in reactive astrocytes of the ipsilateral GP in the middle stage, but not different from the control rats in the later stage of the pathological process in 6-OHDA lesioned rats. Furthermore, the down-regulation of Nav1.6 expression in the ipsilateral GP can significantly improve motor deficits in 6-OHDA lesioned rats in the middle stage of the pathological process. The electrophysiological experiments show that the down-regulation of Nav1.6 expression in the ipsilateral GP significantly decreases the abnormal high synchronization between the ipsilateral M1 (the primary motor cortex) and GP in 6-OHDA lesioned rats. Ca2+ imaging reveals that the down-regulation of Nav1.6 expression reduces the intracellular concentration of Ca2+ ([Ca2+ ]i) in primary cultured astrocytes. These findings suggest that the increased Nav1.6 expression of reactive astrocytes in the GP play an important role in the pathogenesis of motor dysfunction in the middle stage in 6-OHDA lesioned rats, which may participate in astrocyte-neuron communication by regulating [Ca2+ ]i of astrocytes, thereby contributing to the formation of abnormal electrical signals of the basal ganglia (BG) in 6-OHDA lesioned rats.

Fluoxetine tunes the abnormal hippocampal oscillations in association with cognitive impairments in 6-OHDA lesioned rats.

Cognitive decline is a common clinical symptom in Parkinson's disease (PD) patients. Fluoxetine (FLU), a selective serotonin reuptake inhibitor, can improve cognitive deficits in demented patients. The present study investigated the effects of FLU on spatial learning and memory cognitions in 6-OHDA lesioned rats. Morris water maze (MWM) test showed that FLU significantly improved spatial cognitive deficits in rats with unilateral 6-OHDA injection at 4 and 7 weeks after 6-OHDA injection. Electrophysiological recordings demonstrated that the number and duration of high voltage spindles(HVSs)in the ipsilateral hippocampus of 6-OHDA lesioned rats were decreased by the administration of FLU. Furthermore, the spectral analysis of per frequency revealed increases in δ and θ rhythm power and decreases in α, ß and γ rhythm power in the ipsilateral hippocampus of 6-OHDA lesioned rats in contrast to the saline-treated rats. Acute FLU treatment can reduce δ and θ rhythm power, and enhance α, ß and γ rhythm power in the ipsilateral hippocampus of 6-OHDA lesioned rats. These findings suggest that FLU improves impaired cognition by tuning oscillatory activities in the hippocampus of 6-OHDA lesioned rats.

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

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.