Elucidation of neurological disoders in neonatal jaaundice

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07844
• 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: Shimane University
• Principal Investigator: Arata Oh-Nishi 島根大学, 医学部, 客員教授 (00507014)
• Co-Investigator(Kenkyū-buntansha): 横田 茂文 島根大学, 学術研究院医学・看護学系, 准教授 (50294369)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ビリルビン代謝 / BIND / セロトニン / 脳神経障害 / ADHD / 統合失調症

Outline of Final Research Achievements

Epidemiological studies have suggested that even bilirubin metabolism abnormalities that do not cause kernicterus can impair neurodevelopment, which is at risk for developing psychiatric disorders such as ADHD and schizophrenia from early childhood to late adolescence. Hence a novel disease concept, Bilirubin Induced Neurological Disorders; BIND has been suggested. However, the pathophysiology of BIND remains largely unknown, and effective treatment has not yet been established. In this study, we analyzed the brain dysfunction in an animal model of BIND (Gunn rat) in detail and searched for potential therapeutic agents. As a result, it was clarified that the physiological brain dysfunction of serotonin hyper-transmission is behind the cognitive behavioral disorder in Gunn rats, and the possibility that eltoprazine may respond to the disease based on this dysfunctional mechanism was demonstrated.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

軽度のビリルビン代謝異常によって引き起こされる脳神経障害（BIND）について不明である点が多いため、有効な治療法が確立していない。更にBINDを引き起こす遺伝子異常が日本人において多いと推定されている。本研究で、このビリルビン代謝障害によって脳内セロトニン伝達障害が起こることをモデル動物で明らかにし、エルトプラジンという低分子化合物が当該脳神経障害の治療薬になる可能性を示した。エルトプラジンはヒトでの安全性が確認されている化合物であることから臨床応用が期待される。