Magnesium regulates neural stem cell proliferation in the mouse hippocampus by altering mitochondrial function

Abstract

In the adult brain, neural stem cells from the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the cortex progress through the following five developmental stages: radial glia-like cells, neural progenitor cells, neuroblasts, immature neurons, and mature neurons. These developmental stages are linked to both neuronal microenvironments and energy metabolism. Neurogenesis is restricted and has been demonstrated to arise from tissue microenvironments. We determined that magnesium, a key nutrient in cellular energy metabolism, affects neural stem cell (NSC) proliferation in cells derived from the embryonic hippocampus by influencing mitochondrial function. Densities of proliferating cells and NSCs both showed their highest values at 0.8 mM [Mg(2+) ]o , whereas lower proliferation rates were observed at 0.4 and 1.4 mM [Mg(2+) ]o . The numbers and sizes of the neurospheres reached the maximum at 0.8 mM [Mg(2+) ]o and were weaker under both low (0.4 mM) and high (1.4 mM) concentrations of magnesium. In vitro experimental evidence demonstrates that extracellular magnesium regulates the number of cultured hippocampal NSCs, affecting both magnesium homeostasis and mitochondrial function. Our findings indicate that the effect of [Mg(2+) ]o on NSC proliferation may lie downstream of alterations in mitochondrial function because mitochondrial membrane potential was highest in the NSCs in the moderate [Mg(2+) ]o (0.8 mM) group and lower in both the low (0.4 mM) and high (1.4 mM) [Mg(2+) ]o groups. Overall, these findings demonstrate a new function for magnesium in the brain in the regulation of hippocampal neural stem cells: affecting their cellular energy metabolism.