The low survival and differentiation rates of stem cells after either
transplantation or neural injury have been a major concern of stem cell-based
therapy. Thus, further understanding long-term survival and differentiation of stem cells may uncover new targets for discovery and development of novel therapeutic approaches. We have previously described the impact of mitochondrial apoptosis-related events in modulating neural stem cell (NSC) fate. In addition, the endogenous
bile acid,
tauroursodeoxycholic acid (
TUDCA) was shown to be neuroprotective in several animal models of
neurodegenerative disorders by acting as an anti-apoptotic and
anti-oxidant molecule at the mitochondrial level. Here, we hypothesize that
TUDCA might also play a role on NSC fate decision. We found that
TUDCA prevents mitochondrial apoptotic events typical of early-stage mouse NSC differentiation, preserves mitochondrial integrity and function, while enhancing self-renewal potential and accelerating cell cycle exit of NSCs. Interestingly,
TUDCA prevention of mitochondrial alterations interfered with NSC differentiation potential by favoring neuronal rather than astroglial conversion. Finally, inhibition of mitochondrial
reactive oxygen species (mtROS) scavenger and
adenosine triphosphate (
ATP) synthase revealed that the effect of
TUDCA is dependent on mtROS and
ATP regulation levels. Collectively, these data underline the importance of mitochondrial stress control of NSC fate decision and support a new role for
TUDCA in this process.