In vitro effects of H₂O₂ on neural stem cell differentiation

The development of the CNS is a complex and well-regulated process, where stem cells differentiate into committed cells depending on the stimuli from the microenvironment. Alterations of oxygen levels were stated to be significant in terms of brain development and neurogenesis during embryonic development, as well as the adult neurogenesis. As a product of oxygen processing, hydrogen peroxide (H₂O₂) has been established as a key regulator, acting as a secondary messenger, of signal transduction and cellular biological functions. H₂O₂ is involved in survival, proliferation, and differentiation of neural stem cells into committed cells of the CNS. Effects of different concentrations of exogenous H₂O₂ on neuronal differentiation and the molecular pathways involved are yet to be clearly understood. Here, we investigated the concentration-dependent effects of H₂O₂ on differentiation of neural stem cells using CGR8 embryonic mouse stem cell line. We have demonstrated that treated doses of H₂O₂ suppress neural differentiation; additionally, our study suggests that relatively high doses of exogenous H₂O₂ suppress the differentiation process of neural stem cells through AKT and p38 pathways.