Early-life midazolam exposure persistently changes chromatin accessibility to impair adult hippocampal neurogenesis and cognition

Hiroyoshi Doi, Taito Matsuda, Atsuhiko Sakai, Shuzo Matsubara, Sumio Hoka, Ken Yamaura, Kinichi Nakashima

Research output: Contribution to journalArticlepeer-review

Abstract

Linkage between early-life exposure to anesthesia and subsequent learning disabilities is of great concern to children and their families. Here we show that early-life exposure to midazolam (MDZ), a widely used drug in pediatric anesthesia, persistently alters chromatin accessibility and the expression of quiescence-associated genes in neural stem cells (NSCs) in the mouse hippocampus. The alterations led to a sustained restriction of NSC proliferation toward adulthood, resulting in a reduction of neurogenesis that was associated with the impairment of hippocampal-dependent memory functions. Moreover, we found that voluntary exercise restored hippocampal neurogenesis, normalized the MDZ-perturbed transcriptome, and ameliorated cognitive ability in MDZ-exposed mice. Our findings thus explain how pediatric anesthesia provokes long-term adverse effects on brain function and provide a possible therapeutic strategy for countering them.

Original languageEnglish
Article numbere2107596118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number38
DOIs
Publication statusPublished - Sep 21 2021

All Science Journal Classification (ASJC) codes

  • General

Fingerprint

Dive into the research topics of 'Early-life midazolam exposure persistently changes chromatin accessibility to impair adult hippocampal neurogenesis and cognition'. Together they form a unique fingerprint.

Cite this