Lithium chloride promotes neuronal differentiation of rat neural stem cells and enhances neural regeneration in Parkinson’s disease model

摘要

Parkinson’s disease (PD) is one of the most common neural degenerative disease, affecting millions of people globally. Great progress has been made in the PD treatment, and one of the most promising one is the stem cell-based therapy. Thus, studies on the differentiation of neural stem cells (NSCs) are important to the advancement in PD therapy. In this study, we used the rat NSCs to elucidate the role of Lithium in the proliferation and differentiation of NSCs by immunostaining against Ki67 and BrdU analysis as well as immunostaining against specific neuronal markers. We concluded that lithium chloride (LiCl) treatment could enhance the proliferation in NSCs and promote the dopaminergic neuronal differentiation of NSCs in vitro. This process was potentially mediated by Wnt signaling pathway. Using the 6-OHDA-induced PD models, we provided evidence to show that LiCl had the capacity to enhance the proliferation in NSCs and differentiation towards dopaminergic neurons in vivo. The beneficial effect of LiCl treatment was further validated by the fact that the motor function as well as learning and memory was improved in the PD models through Rotarod test and Morris water maze analysis. The learning and memory improvement was further supported by the increase in dendrite spine density in PD models receiving LiCl-treated NSCs. Through this study, we concluded that Lithium plays an important role in promoting NSCs’ neuronal differentiation in vitro and improving the symptoms of PD models in vivo. It is of great significance that this work showed the potential application of Lithium in the PD therapy in the future.