Neural stem cell-specific deletion of Atg7 alleviates hippocampal dysfunction and neuronal alterations induced by chronic restraint stress.

Adult hippocampal neurogenesis is inhibited by chronic psychological stress and impaired neurogenesis underlies stress-related psychological disorders. We previously reported that chronic restraint stress (CRS) evokes autophagic death of adult hippocampal neural stem cells (NSCs) while NSC-specific deletion of Atg7 prevents death of NSCs. Examination of cognitive ability and mood regulation next day of the termination of stress showed normal hippocampal function in mice deficient of Atg7. However, it was not investigated whether the preservation of NSC pool alleviates hippocampal neuronal alterations. Here, we show that CRS increased c-Fos-positive, activated neurons in the granule cell layer and decreased spine density of CA3 neurons in the hippocampus, and these hippocampal neuronal deficits were prevented by NSC-specific deletion of Atg7. Of note, our observation was conducted right after the termination of CRS. Therefore, our results suggest that the detrimental effects of stress on hippocampal neurons can be buffered by NSCs independent of neurogenesis and NSCs are essential to the hippocampal function both through the neurogenesis-dependent developmental process and by direct regulation of neural activation.