Identifying molecular mechanisms and peripheral biomarkers of cognitive impairment in offspring from diabetic mother (ODM)

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K24039
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Tokyo Medical University
• Principal Investigator: SASAKI Toru 東京医科大学, 医学部, 講師 (30421001)
• Project Period (FY): 2019-08-30 – 2024-03-31
• Keywords: 母体耐糖能異常 / 認知機能障害 / 末梢血中バイオマーカー / トランスクリプトーム解析 / GLP-1受容体

Outline of Final Research Achievements

We created a mouse model of STZ-induced diabetes mellitus complicated pregnancy and identified learning disabilities in its offspring (ODM). Furthermore, we confirmed that there is specific expression of GLP-1 receptors in the prefrontal cortex, which is involved in cognitive function, that there is expression of GLP-1 receptors in parts of the placenta, and that maternal administration of GLP-1 receptor agonists improves cognitive dysfunction in ODMs. In addition, transcriptome analysis of peripheral blood leukocytes was performed to identify novel biomarkers for learning disabilities in ODM. The correlation between the differential expressed genes and the motor learning index obtained from the accelerated rotarod test was evaluated using ensemble machine learning, and an AI-based prediction model for learning disabilities was also constructed.

Free Research Field

産科婦人科学

Academic Significance and Societal Importance of the Research Achievements

妊娠中の母体耐糖能異常は児（ODM）に認知機能障害をもたらすことが知られているが、その分子生物学的機序は明らかでなく、早期医学的介入を可能とするバイオマーカーも同定されていない。
本研究ではマウスODMにおける認知機能障害の分子生物学的機序の一端を明らかとし、母体へのGLP-1受容体アゴニスト投与がODMの認知機能障害を改善することを確認した。また、ODMの認知機能障害に対して出生早期から医学的介入を可能とし得る新規バイオマーカーの予測モデルを構築した。本研究で得られた新たな知見は、マウスのみならずヒトへの臨床応用の可能性を十分に有しており、その学術的、社会的意義は非常に高いものと思われる。