Mechanisms of RNA Splicing Selection Abnormality Induced by Inflammation in the Brain Causing Behavioral Abnormalities Related to Psychiatric Diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 19H03538
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 51020:Cognitive and brain science-related
• Research Institution: University of Toyama
• Principal Investigator: TAKAO Keizo 富山大学, 学術研究部医学系, 教授 (80420397)
• Co-Investigator(Kenkyū-buntansha): 吉田 知之 富山大学, 学術研究部医学系, 准教授 (90372367)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 胎生期ストレス / 自閉症 / RNA編集 / シナプス / 炎症

Outline of Final Research Achievements

Autistic-like behavioral abnormalities were observed in the pups of the maternal inflammation model, and analysis of the embryonic brain revealed a PTPδ microexon selection pattern in the cortex that was different from that of the control group. Although behavioral abnormalities were also observed in the pups of systemic lupus erythematosus model mice, no obvious difference was detected in PTPδ microexon selection in the prenatal brain compared to the control group. This suggests that prenatal brain inflammation caused by maternal inflammation leads to abnormal behavior and PTPδ microexon selection in the cerebral cortex, but that chronic inflammation results in behavioral abnormalities through a different mechanism.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

自閉症など高次脳機能が関わる疾患は成長するまで分かりにくく、また根本的な治療が難しい。本研究は脳発達期における RNA 編集異常がシナプス結合選択の異常をもたらし、それが高次脳機能異常を伴う発達障害の原因であるという仮説に基づき、どのような因子がRNA 編集異常とシナプス結合選択の異常をもたらすのか同定し、その制御機構を明らかにすることを試みた。母体の炎症によって産仔に発達障害様の行動異常が引き起こされるのと平行して胎児期の脳でシナプスオーガナイザーの微小エクソン選択の異常が生じていることが明らかとなった。これらの成果は発達障害の発症メカニズムや治療法の開発に貢献するものと考えられる。