Analysis of pathological mechanism of cognitive impairment and neurodevelopmental disorder observed in the new model mouse of extremely preterm infants

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07855
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Keio University
• Principal Investigator: DEGUCHI Kimiko 慶應義塾大学, 医学部(信濃町), 講師(非常勤) (50227542)
• Co-Investigator(Kenkyū-buntansha): 久保 健一郎 慶應義塾大学, 医学部(信濃町), 准教授 (20348791)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 超早産児 / 虚血性脳障害 / 神経学的後遺症 / 認知機能障害 / 自閉スペクトラム症 / 注意欠如多動症 / 発達神経症 / 細胞移動

Outline of Final Research Achievements

In this study, we used our unique mouse model of ischemic brain damage, in which cognitive impairments occur after birth by temporarily occluding the uterine arteries in pregnant mice. This mouse model is considered as a good model for the neurological impairments of ischemic brain damage in extremely preterm infants. We analyzed whether impaired neuronal migrations caused by ischemic brain damage during development result in morphological changes in spines after birth. Furthermore, we analyzed the changes in gene expression profiles of neurons that show impaired migrations. As a result of transcriptome analysis using next generation sequencing and microarray analysis, changes in gene expression profiles were detected in molecular pathways related to cognitive functions. These changes might underlie cognitive impairments in extremely preterm infants and would be important as candidates for future therapeutic targets.

Free Research Field

小児科学

Academic Significance and Societal Importance of the Research Achievements

超早産児の虚血性脳障害による神経学的後遺症の特徴としては、これまでのような脳性麻痺などの運動発達障害が主体ではなく、認知機能障害や、自閉スペクトラム症や注意欠如多動症のような発達神経症（発達障害）の頻度が高い事が注目されている。本研究によって、発達段階における虚血性脳障害という環境要因によって、認知機能に関わる分子経路の遺伝子発現が変化して、これが生後の認知機能障害に関わる可能性が示された。これらの分子経路は、治療標的の候補となるため、今後、超早産児の虚血性脳障害による神経学的後遺症に対する治療開発を進めていく上で、基盤となる重要な所見が得られた。