Elucidation of role of NOX1/NADPH oxidase in the development of neurodevelopment disorders.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07087
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Kinjo Gakuin University (2021-2023); Kyoto Prefectural University of Medicine (2020)
• Principal Investigator: Ibi Masakazu 金城学院大学, 薬学部, 准教授 (10336539)
• Co-Investigator(Kenkyū-buntansha): 浅岡 希美 京都府立医科大学, 医学(系)研究科(研究院), 助教 (90826091)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 発達障害 / 活性酸素種

Outline of Final Research Achievements

In this study, we investigated the role of NOX1/NADPH oxidase, an enzyme generating reactive oxygen species, in the development of ASD using Nox1-deficient mice (Nox1-KO). In the MIA model of gestational polyinosinic-polycytidylic acid (poly(I:C)) exposure, impairment of social preference and defects in motor coordination were observed in WT offspring but not in offspring deficient in Nox1. MIA up-regulated NOX1 mRNA in the cerebral cortex and cerebellum of the fetus but not in the adult offspring. Moreover, the dropout of Purkinje cells in lobule VII of MIA-affected offspring was significantly ameliorated in Nox1KO. Taken together, these results suggested that NOX1/NADPH oxidase plays an essential role in some behavioral phenotypes observed in ASD, possibly by promoting the loss of Purkinje cells in the cerebellum.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

精神疾患は、遺伝要因と環境要因が相互作用して発症する高次脳機能障害である。近年その罹患率は増加しており、本疾患の克服が喫緊の課題となっている。本研究により、ASDの新たな発症機序に活性酸素産生酵素のNOX1/NADPHオキシダーゼが重要であることを見出した。本研究結果は、ASDの新たな治療薬開発に基礎的知見を提供できることが示唆された。