Sleep deprivation inhibits proliferation of adult hippocampal neural progenitor cells by a mechanism involving IL-17 and p38 MAPK.

Sleep deprivation impairs hippocampal neurogenesis, but the underlying mechanisms are inadequately understood. Sleep deprivation is associated with an increased production of pro-inflammatory factors. In this study, we demonstrate that acute rapid eye movement (REM) sleep deprivation in mice for 3 days leads to increased expression of interleukin (IL)-17A, IL-17F and activation of p38 MAPK pathway in the hippocampus, together with suppressed cell proliferation in the dentate gyrus. Similarly, activation of p38 MAPK and suppressed cell proliferation in the dentate gyrus were observed after administration of recombinant IL-17 in mice without sleep deprivation. Pharmacological blockade of the p38 MAPK after sleep deprivation mitigates sleep deprivation-induced ablation of cell proliferation in the dentate gyrus with unaltered expression of IL-17A and IL-17F. In addition, hippocampal neural progenitor cells express IL-17 receptor A (IL-17RA) and IL-17 receptor C (IL-17RC). These findings suggest that acute REM sleep deprivation suppresses proliferation of adult hippocampal neural progenitor cells by a mechanism involving IL-17 and p38 MAPK signaling.