Mechanisms of nutrient homeostasis and cognitive functions through metabolic pathways in glial cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H04137
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: National Center for Geriatrics and Gerontology
• Principal Investigator: Taguchi Akiko 国立研究開発法人国立長寿医療研究センター, 研究所 ジェロサイエンス研究センター, 部長 (80517186)
• Co-Investigator(Kenkyū-buntansha): 王 蔚 国立研究開発法人国立長寿医療研究センター, 統合加齢神経科学研究部, 研究員 (00845167)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: インスリンシグナル / アストロサイト / 認知機能 / 栄養エネルギー代謝 / トランスポーター / 耐糖能 / 老化

Outline of Final Research Achievements

We have found that (1) abnormal glucose tolerance occurred in young deficient mice, (2) decreased hippocampal neurogenesis and impaired spatial memory were observed, (3) age-like morphological changes were observed in astrocytes, (4) significant expression changes were observed for mitochondria-related factors, (5) aberrant activation changes of factor-related to insulin signaling were observed in skeletal muscle, (6) significant changes in various transporters and lactate were observed in the nutrient energy transport pathway in the brain, and (7) no changes in glucose tolerance were observed in old age. These results indicate that the astrocyte IRS1 is involved in the regulation of systematic glucose metabolism and cognitive function, and that its function may change with age.

Free Research Field

神経内分泌

Academic Significance and Societal Importance of the Research Achievements

本研究は、新規作製した変異マウスの解析を通じて、アストロサイトIRS1が関与する新たな栄養エネルギー代謝・認知機能調節機構の可能性に迫るもので、学術的独自性が高い内容である。本研究成果において、従来の認知症研究では発見されなかった新たな代謝・認知機能調節機序の存在が示唆されたことから、認知機能障害の予防・治療法の開発へと発展することに期待がもたれる。