The effect of endoplasmic reticulum stress on neurotoxicity caused by inhalational anesthetics

Research Project

Project/Area Number	25861359
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Anesthesiology
Research Institution	Chiba University
Principal Investigator	KOMITA Mari 千葉大学, 医学部附属病院, 助教 (90589194)
Co-Investigator(Kenkyū-buntansha)	AOE Tomohiko 千葉大学, 医学研究院, 准教授 (90311612)
Project Period (FY)	2013-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000) Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords	神経科学 / ストレス / アポトーシス / 神経細胞 / 小胞体ストレス / 麻酔薬
Outline of Final Research Achievements	Background: The mechanisms by which inhalational anesthetics cause neurotoxicity are not well clarified. Since ER stress leads to cellular dysfunction and apoptotic cell death, leading to diverse human disorders such as neurodegenerative diseases, we hypothesized ER stress may play a role in neurotoxicity caused by inhalational anesthetics. Results,Conclusions: Sevoflurane exposure cause ER stress, which is tolerated to some extent in the wild type cells. When this tolerance is limited, like in cells with mutant BiP, the exposure leads to cell death in the brain, indicating that ER stress may partially mediate neurotoxicity caused by inhalational anesthetics. This study conceivable that the patients with certain conditions sensitive to ER stress such as ischemia, hypoxia, developing brain or neurodegenerative diseases may be vulnerable to inhalational anesthetics.