The D1R-specific NSF deficient mice as a novel schizophrenic model

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06752
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: University of Fukui
• Principal Investigator: Xie MinJue 福井大学, 子どものこころの発達研究センター, 助教 (40444210)
• Co-Investigator(Kenkyū-buntansha): 松崎 秀夫 福井大学, 子どものこころの発達研究センター, 教授 (00334970) ; 村田 航志 福井大学, 学術研究院医学系部門, 助教 (10631913)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: NSF / dopamine / dopamine receptor / schizophrenic model

Outline of Final Research Achievements

In the present study, we generated the D1R-specific Nsf conditional knockout mice (D1R-NSFcKO mice) and investigated their behavioral, neurotransmitter, and neurophysiological phenotypes in vivo. D1R-NSFcKO mice exhibited the abnormal spontaneous rotation behaviors and high locomotion activity. The dopamine D2 receptor antagonist sulpiride suppressed the hyperactive in D1R-NSFcKO mice. We investigated the startle habituation and prepulse inhibition (PPI) test, and found that both startle habituation and PPI were impaired in D1R-NSFcKO mice. In addition, we found that dopamine was significantly increased in the striatum of D1R-NSFcKO mice compared with that of control mice. These findings demonstrate that Nsf plays a role in motor activation and sensorimotor gating via regulating the dopamine and dopamine receptor. D1R-NSFcKO mice exhibited locomotor up-regulation and a defect in sensorimotor gating, resembling the behavioral phenotype of schizophrenia.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

我々が着目したNSFの機能異常は、統合失調症の発症メカニズムを包括的に理解する鍵の分子となる可能性がある。また、 D1R-NSF cKOマウスのレスキュー実験によって脳内D1Rの発現低下が新たな統合失調症の治療標的候補となれば、統合失調症の新規治療法開発に道が開かれる。さらに、本研究成果から得られる知見は、運動・認知の情報処理や情動の制御機能を支える基本原理の理解にも貢献が十分に期待できる。