Metabolic state alteration of neural stem cells controls FAS-mediated apoptosis and neurogenesis

Abstract

Metabolic stress causes an increased Fas-FasL (recep tor-ligand pair) expression in Neural Stem Cells (NSCs) leading to Fas-induced apoptosis. In this study, we discuss the exposure of NSCs to different metabolic treatments that provoke cellular stress responses. We demonstrate that challenging cultured NSCs to ethanol (ETOH) increased cellular death via Fas-mediated apoptosis. Moreover, we establish that NSCs cultured under low lipid conditions, in which they were deprived of essential fatty acids, demonstrated increased cellular survival rates suggesting an increased ability for these lipid-starved cells to endure a stressed environment. This was further confirmed by exposing NSCs to low glucose levels and observing a decrease in percent death in low lipid NSCs. When stressed, NSCs have increased reactive oxygen levels and are susceptible to apoptosis. These findings indicate that under starved and stressed conditions, and in the presence of Fas Ligand (FasL), NSCs pursue fatty acid oxidation by burning fat as fuel. This may be the key to better understand the metabolic states of brain tumors and the characteristics of cancer.