Here we show that early-life exposure to midazolam (MDZ), a widely used drug in pediatric anesthesia, persistently alters chromatin accessibility and expression of quiescence-associated genes in neural stem cells (NSCs) in mouse hippocampus. The alterations led to a continuous restriction of NSC proliferation toward adulthood, resulting in reduction of neurogenesis associated with the impairment of hippocampal-dependent memory functions. Moreover, we found that voluntary exercise restored hippocampal neurogenesis accompanied by the normalization of MDZ-perturbed transcriptome and ameliorated declined cognitive ability in MDZ-exposed mice.

igG, Egr1, Cdknta, Notch2, Hopx, Id4