Yes-Associated Protein Promotes Impaired Proliferation of Hippocampal Neural Stem Cells in Zinc-Deficient Sprague-Dawley Rats

Abstract

Zinc deficiency results in abnormal brain development and dysfunction, although the precise molecular mechanisms underlying these observations remain unclear. In this study, we aimed to investigate the mechanisms underlying impaired hippocampal neural stem cell (NSC) proliferation observed in zinc-deficient Sprague-Dawley (SD) rats. Zinc-deficiency was associated with reduced expression of co-localizing Yes-associated protein (YAP) and cyclin D1 in NSCs in hippocampal tissue. Moreover, we observed a significant reduction in the ratio of proliferating hippocampal NSCs in rats maintained on zinc-deficient diets. Reduced proliferation was also observed in immortalized C17.2 NSCs exposed to N, N, N′, N′ -Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN); these findings were associated with diminished expression of both YAP and cyclin D1. Overexpression of YAP rescued the C17.2 cells from zinc-deficiency-induced reductions in cyclin D1 expression as well as impaired proliferation. Taken together, these results demonstrate that downregulation of YAP contributes to impaired proliferation of NSCs observed in response to zinc-deficient.