Elucidation of the effects of impaired glucose tolerance in the brain on postoperative cognitive dysfunction and establishment of its preventive methods

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08833
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Himeji Dokkyo University
• Principal Investigator: Yamamoto Naoki 姫路獨協大学, 薬学部, 教授 (90393157)
• Co-Investigator(Kenkyū-buntansha): 祖父江 和哉 名古屋市立大学, 医薬学総合研究院(医学), 教授 (90264738)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 糖尿病 / 麻酔薬 / 術後認知機能

Outline of Final Research Achievements

1. In the type 2 DM model TSOD mice, we investigated the activation of insulin-related intracellular signal transduction system in order to confirm the abnormal glucose tolerance in the mice before administration of inhalation anesthetic. As a result, it was found that the PI3 kinase pathway, which is one of the insulin signal transduction systems of the whole brain, decreases with aging. We are currently reassessing cognitive decline after inhalational anesthetic administration using a new object recognition test and a Y-maze test.
2. It was found that it regulates in astrocytes (primary culture) on the expression of neprilysin and insulin degrading enzymes, which are Aβ-degrading enzymes, by activating the signals of protein kinases A and C, which play important roles in the intracellular signal transduction system in the brain. It was also clarified that this regulated expression also regulates the degradation of Aβ by astrocytes. (Neurosci Res. 2020)

Free Research Field

神経化学

Academic Significance and Societal Importance of the Research Achievements

アジア系人種の特徴を有する2型糖尿病（DM）モデルのTSOD（Tsumura Suzuki Obese Diabetes）マウスに吸入麻酔薬を投与することによって、脳全体のインスリンシグナル伝達系の一つであるPI3kinase経路が低下しており、この経路の下流にはアルツハイマー病発症に大きく関わるタウタンパクのリン酸化の調節機構がある。この結果によって、吸入麻酔薬投与後の脳内耐糖能異常とPOCDの因果関係を解明する手がかりを掴めると考える。