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

Proceedings of the National Academy of Sciences of the United States of America
Hiroyoshi DoiKinichi Nakashima

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.

References

May 1, 1992·Science·J J Kim, M S Fanselow
Jun 6, 2000·Brain & Development·H YoshikawaY Oda
Jan 8, 2004·The Journal of Cell Biology·Jenny HsiehFred H Gage
Sep 24, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Henriette van PraagFred H Gage
Feb 26, 2008·Cell·Chunmei ZhaoFred H Gage
Sep 19, 2008·Genome Biology·Yong ZhangX Shirley Liu
May 22, 2009·Nucleic Acids Research·Timothy L BaileyWilliam S Noble
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Dec 4, 2009·Anesthesia and Analgesia·Catherine E Creeley, John W Olney
May 4, 2010·Nature Biotechnology·Cory Y McLeanGill Bejerano
Nov 2, 2011·Experimental Animals·Sumiko KawaiTsutomu Kurosawa
Mar 6, 2012·Nature Methods·Ben Langmead, Steven L Salzberg
Apr 10, 2013·Proceedings of the National Academy of Sciences of the United States of America·Alexandra VeyracSerge Laroche
Aug 22, 2013·Genes & Development·Ben MartynogaFrançois Guillemot
Oct 8, 2014·Physiological Reviews·James B AimoneFred H Gage
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Jan 7, 2015·Current Protocols in Molecular Biology·Jason D BuenrostroWilliam J Greenleaf
Nov 26, 2015·Life Sciences·Sulagna Dutta, Pallav Sengupta
Oct 19, 2016·Nature Reviews. Neuroscience·Laszlo Vutskits, Zhongcong Xie
May 26, 2017·Genome Research·Jonathan A BeaganJennifer E Phillips-Cremins
Nov 22, 2017·British Journal of Anaesthesia·C J WeirJ J Lambert
Jan 13, 2018·Nature Structural & Molecular Biology·H Courtney HodgesGerald R Crabtree
Apr 4, 2018·Proceedings of the National Academy of Sciences of the United States of America·Atsuhiko SakaiKinichi Nakashima

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