Effects of general anesthetics on the regulatory mechanisms of neuronal development in the critical period
Project/Area Number |
15H04970
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Anesthesiology
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Research Institution | National Defense Medical College |
Principal Investigator |
SATOH YASUSHI 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 薬理学, 准教授 (10505267)
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Co-Investigator(Kenkyū-buntansha) |
後藤 典子 金沢大学, がん進展制御研究所, 教授 (10251448)
福田 敦夫 浜松医科大学, 医学部, 教授 (50254272)
遠藤 昌吾 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (60192514)
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
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Keywords | ERK / general anesthetics / apoptosis / developing brain / toxicity / mouse / sevoflurane / 全身麻酔薬 / 発達期 / 神経毒性 / セボフルラン / 自閉症 / 臨界期 / マウス / 神経発達 / 吸入麻酔薬 / ノックアウトマウス / 神経回路 / 発達 / 麻酔 / 神経 / ERK / 細胞内情報伝達 / アポトーシス |
Outline of Final Research Achievements |
In animal models, neonatal exposure to general anesthetics significantly increased neuronal apoptosis with subsequent behavioral deficits in adulthood. Here we investigated the causal relationship of decreased phosphorylation of extracellular signal-regulated kinases (ERKs) and anesthetic-induced toxicity in the developing brain. At postnatal day 6 (P6), mice were exposed to sevoflurane (2%) or the blood-brain barrier-penetrating MEK inhibitor, (SL327) (50 mg/kg). Sevoflurane induced the decrease of ERK phosphorylation. Transient suppression of ERK phosphorylation by an intraperitoneal injection of SL327 at P6 significantly increased apoptosis similar to sevoflurane-induced apoptosis. Conversely, SL327 administration at P14 or P21 did not induce apoptosis, even though ERK phosphorylation was inhibited. Together, our results strongly suggests that suppressed ERK phosphorylation is critically involved in the mechanism underlying anesthetic-induced toxicity in the developing brain.
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] BK channels in microglia are required for2016
Author(s)
Yoshinori Hayashi, Saori Morinaga, Jing Zhang, Yasushi Satoh, Andrea Meredith, Takahiro Nakata, Zhou Wu, Shinichi Kohsaka, Kazuhide Inoue, Hiroshi Nakanishi
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Journal Title
Nature communications
Volume: 7
Issue: 1
Pages: 11697-11697
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] 脳と水素2016
Author(s)
佐藤泰司
Organizer
第20回日本医療ガス学会学術大会
Place of Presentation
秋田
Year and Date
2016-10-15
Related Report
Invited
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