Development of a novel animal model for autism spectrum disorder forcusing on cannabinoid CB1 receptor

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16019
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Nagasaki International University
• Principal Investigator: Nawata Yoko 長崎国際大学, 薬学部, 講師 (00435140)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 自閉スペクトラム症 / 動物モデル / カンナビノイド / オキシトシン / コルチコステロン

Outline of Final Research Achievements

We found that CB1KO mice demonstrated reduced sociability and elevated repetitive grooming behaviors compared to wild-type mice. We next measured serum corticosterone and serum/brain oxytocin, expected as biomarkers for ASD. As a result, serum corticosterone significantly increased in CB1KO mice. In contrast, both serum oxytocin were decreased in CB1KO mice. Based on these results, we next attempted to recover the autistic-like behaviors in CB1KO mice. Then, single administration of an oxytocin receptor agonist, or a type 1 corticotropin-releasing factor (CRF1) receptor antagonist, significantly ameliorated the decrease of sociability and elevated repetitive behaviors in CB1KO mice. Therefore, CB1KO mice could have potential as a novel ASD model mouse and provide possibilities of drug development for ASD using the oxytocin receptor agonist and CRF1 receptor antagonist.

Free Research Field

CB1

Academic Significance and Societal Importance of the Research Achievements

これまで自閉スペクトラム症（ASD）のストレスシステム異常に基づく動物モデルは皆無であった。本研究成果によりカンナビノイドCB1受容体遺伝子欠損（CB1KO）マウスは、行動学的及び生化学観点からストレスシステム異常を示す新規ASDモデル動物となり得る可能性が示され、この点に本研究の学術的意義がある。また、オキシトシン受容体作動薬及び、コルチコトロピン放出因子（CRF）-1受容体拮抗薬はCB1KOマウスのASD様行動を改善することが明らかになった。中核症状に対する根本的治療薬がないASDにおいて、今後の有望な創薬ターゲットを提供出来た点に社会的意義がある。