Kyushu University Academic Staff Educational and Research Activities Database
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Doi Hiroyoshi Last modified date:2022.06.10

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Academic Degree
Faculty of Medicine, Osaka University, Department of Anesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University
Country of degree conferring institution (Overseas)
Yes Doctor
Field of Specialization
ORCID(Open Researcher and Contributor ID)
Total Priod of education and research career in the foreign country
Research Interests
  • Elucidation of molecular mechanisms underlying cognitive decline at adult stage induced by neonatal exposure to midazolam and development of a therapeutic strategy
    keyword : early-life exposure to anesthesia , delayed neurocognitive impairment
Academic Activities
1. Hiroyoshi Doi, Taito Matsuda, Atsuhiko Sakai, Shuzo Matsubara, Sumio Hoka, Ken Yamaura, Kinichi Nakashima, 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, 10.1073/pnas.2107596118, 118, 38, 2021.09, 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..