Effects of high glucose concentrations on the expression of genes involved in proliferation and cell-fate specification of mouse embryonic neural stem cells

Abstract

Maternal diabetes induces neural tube defects (NTD) during embryogenesis. Since neural tube is derived from neural stem cells (NSCs), it is hypothesized that the NTD in diabetic pregnancy result from altered expression of developmental control genes, leading to abnormal proliferation and cell fate choice of NSCs. In the present study, the cell viability, proliferation and differentiation of NSCs exposed to physiological or high glucose concentration (PG or HG) medium were examined. Expression of developmental control genes was also analyzed. HG decreased the proliferation of NSCs and accelerated the neuronal and glial differentiation from NSCs. Exposure to HG altered the expression levels of Shh, Bmp4, Neurog1/2, Ascl1, Hes1, Dll1 and Olig1 in NSCs. Moreover, HG perturbed the glucose uptake and induced oxidative stress by altering the polyol pathway of glucose metabolism, leading to abnormal cell cycle progression in NSCs. These changes may form the basis for NTDs observed in embryos of diabetic pregnancy.