Elucidation of the mechanism of postoperative cognitive dysfunction through epigenetics

• Project/Area Number: 15K20051
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Sapporo Medical University
• Principal Investigator: Tachibana Shunsuke 札幌医科大学, 医学部, 研究員 (30737309)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 術後認知機能障害 / 手術ストレス / トランスクリプトーム解析 / デクスメデトミジン / 術後認知機能低下 / 麻酔手術ストレス / 海馬 / 術後認知機能 / セボフルラン

Outline of Final Research Achievements

We performed transcriptomic analysis and comprehensively analyzed the expression changes of messenger RNA (mRNA) in the brain, especially in the hippocampus due to surgery and anesthesia stress. Furthermore, we identified the all expression genes that increased or decreased by surgery and anesthesia stress, and also found that the expression of a specific gene changes in conjunction with the deterioration of cognitive function examined in the Burns Maze test.
In this study, we were able to elucidate a part of the mechanism of post oeprative cognitive dysfunction (POCD), and clarify the specify mRNA as a marker that could predict the onset of cognitive dysfunction.
And, we believe that the information provided from this research will bring significant meaning to future research.

Academic Significance and Societal Importance of the Research Achievements

術後認知機能障害の一つの機序を解明することができた。これらの結果から、予防法の確立も期待することができる。
実際の臨床現場においても、認知機能低下を予防するための戦略を立てることができ、医療費の削減につなげることができる。社会的意義は大変大きい。

Research Products

• [Journal Article] 麻酔科医として術後認知機能障害を俯瞰する (2018)
  • Author(s): 立花俊祐
  • Journal Title: 臨床麻酔 Volume: 7 Pages: 1003-9
• [Presentation] デクスメデトミジンは、高齢マウスにおいて手術侵襲由来のMapt発現増大を抑制し、術後の認知機能低下を減弱する。 (2019)
  • Author(s): 立花俊祐
  • Organizer: 第23回日本神経集中治療学会
• [Presentation] Dexmedetomidine attenuates up-regulation of the Rtn4rl2 gene and restores down-regulation of the Syt1 gene induced by sevoflurane/surgery stress in the hippocampus of elderly mice (2018)
  • Author(s): 立花俊祐
  • Organizer: The European anaesthesiology congress, Euroanaesthesia
  • Int'l Joint Research
• [Presentation] Dexmedetomidine attenuates up-regulation of the Rtn4rl2 gene and restores down-regulation of the Syt1 gene induced by sevoflurane/surgery stress in the hippocampus of elderly mice (2018)
  • Author(s): 立花俊祐、山蔭道明
  • Organizer: Euroanaesthesia 2018
  • Int'l Joint Research
• [Presentation] トランスクリプトーム解析を用いた術後認知機能障害の機序解明 (2016)
  • Author(s): 立花俊祐、早瀬知、山蔭道明
  • Organizer: 日本麻酔科学会第63回学術集会JAシンポジウム：Neuroscience up to date:postoperative cognitive dysfunction
  • Place of Presentation: 福岡
  • Year and Date: 2016-05-27
• [Presentation] Possible Mechanism of Neuroinflammation Induced by Surgical Procedure in the Mouse Hippocampus Determined by Using Transcriptome Analysis (2015)
  • Author(s): Shunsuke Tachibana
  • Organizer: ASA annual meeting
  • Place of Presentation: San Diego,USA
  • Year and Date: 2015-10-24
  • Int'l Joint Research