p38α controls self-renewal and fate decision of neurosphere-forming cells in adult hippocampus

•Neural stem cells (NSC) from the adult hippocampus easily lose their activity in vitro.•Inhibition of p38α enables successful long-term culture of adult hippocampus NSC.•Inhibition of p38α can maintain a high neurogenic capacity for NSC.•Neurogenic competence-related microRNAs are upregulated in NSC by p38α inhibition.•In vitro expanded NSC by p38α inhibition are beneficial against brain damage.

Neural stem cells (NSC) from the adult hippocampus easily lose their activity in vitro. Efficient in vitro expansion of adult hippocampus-derived NSC is important for generation of tools for research and cell therapy. Here, we show that a single copy disruption or pharmacological inhibition of p38α enables successful long-term neurosphere culture of adult mouse hippocampal cells. Expanded neurospheres with high proliferative activity differentiated into the three neuronal lineages under differentiating conditions. Thus, inhibition of p38α can maintain adult hippocampal NSC activity in vitro.