| Project/Area Number |
15K20062
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Anesthesiology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
Higo Shimpei 日本医科大学, 医学部, 講師 (50623922)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | 全身麻酔 / 時計遺伝子 / セボフルラン |
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| Outline of Final Research Achievements |
Surgery under general anesthesia often cause a set of symptoms including sleep and other circadian rhythm disturbances. Our previous studies indicate these rhythm disturbances are caused by the suppression of the expression of a clock gene Per2 in the hypothalamus. The aim of this study is to clarify the molecular mechanisms underling the suppression.
We showed sevoflurane, a commonly used anesthetic, inhibits Per2 expression via GABAergic signal transduction in the suprachiasmatic nucleus, the circadian rhythm center in the hypothalamus.
We also established an in vitro experimental system using a cell line to investigate the detailed mechanisms underlying anesthetic action. This system could be used for the investigation of the effects of other volatile substances on cultured cells. Our experimental system will become a platform for further investigation of the effect of anesthetics on the expression of clock genes.
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| Academic Significance and Societal Importance of the Research Achievements |
手術後に見られるリズム障害・せん妄等はICU症候群・集中治療後症候群と呼ばれ, 術後の予後に重要である. ICU症候群は多種の原因による複合的な症状であるが、睡眠覚醒リズム障害に関しては麻酔の副作用が原因のひとつとして挙げられる. 麻酔がリズム障害の原因となる機序は明らかではなかったが, 本研究により, 視床下部の視交叉上核における時計遺伝子の発現がGABA性の神経シグナル伝達を介して抑制されていることが明らかとなり, ICU症候群予防法の樹立につながることが期待される. また, 気相分子が神経細胞に及ぼす影響を観測するための系を作ったことにより, 将来的な基礎研究につながることが期待できる.
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