Elucidation of the combined mechanism of autism and hearing loss and its application to treatment

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21650
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Nishiyama Masaaki 金沢大学, 医学系, 教授 (50423562)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: 自閉症 / 聴覚障害

Outline of Final Research Achievements

We performed auditory tests such as auditory brainstem response (ABR) and prepulse inhibition (PPI) using Chd8 heterozygous mice, and found that PPI was increased in these mice, and the latency was prolonged in ABR. Therefore, we focused on the function of CHD8 in oligodendrocytes of the auditory conduction path. In the auditory pathway, Chd8 heterozygous mice showed reduced myelination. Furthermore, we generated oligodendrocyte-specific Chd8 heterozygous mice and performed behavioral analysis, and found that some of the behavioral abnormalities observed in whole-body Chd8 heterozygous mice were reproduced.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

これらの結果から、CHD8変異→オリゴデンドロサイト機能異常→聴覚障害→コミュニケーション障害という因果関係が推測され、聴覚障害がコミュニケーション障害の原因であることが示唆された。すでにわれわれは、同責任病変に対して再ミエリン化促進剤や光遺伝学による治療の実験を進めており、自閉症の治療法への応用について検討している。これらの知見は当初の研究目的に適っており、順調に達成されつつあると考えられる。