Lithium chloride promotes proliferation of neural stem cells in vitro, possibly by triggering the Wnt signaling pathway

The objective of this study was to clarify the relationship between the effect and associated mechanisms of lithium chloride on neural stem cells (NSCs) and the Wnt signaling pathway. The expression of key molecules proteins related to the Wnt signaling pathway in the proliferation and differentiation of control NSCs and lithium chloride-treated NSCs was detected by Western blot analysis. Flow cytometry analysis was applied to study the cell cycle dynamics of control NSCs and NSCs treated with lithium chloride. The therapeutic concentrations of lithium chloride stimulated NSC proliferation. β-catenin expression gradually decreased, while Gsk-3β expression gradually increased (P < 0.01). Furthermore, NSCs treated with lithium chloride showed significantly enhanced β-catenin expression and inhibited Gsk-3β expression in a dose-dependent manner. NSCs in the G0/G1-phases were activated with an increased therapeutic concentration of lithium chloride, while NSCs in the S-phase, as well as G2/M-phases, were arrested (P < 0.01). These data confirm that the proliferation of NSCs is remarkably promoted through changes of cell dynamics after treatment with lithium chloride. Our results provide insight into the effects of lithium chloride in promoting the proliferation abilities of NSCs in vitro and preventing the cells from differentiating, which is potentially mediated by activation of the Wnt signaling pathway.