Neural activity-dependent transcription factor Npas4 is required for neuroprotection and survival after stroke

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06465
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Kagawa University
• Principal Investigator: Hiroo Takahashi 香川大学, 医学部, 助教 (20390685)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: Npas4 / 脳梗塞 / 細胞死

Outline of Final Research Achievements

Cerebral infarction is an extremely common disease. This study analyzed the endogenous neuroprotective mechanism activated by cerebral infarction. We found that the transcription factor Npas4, which is known to promote neuronal development in a healthy brain, is strongly induced in cerebral cortical neurons after infarction. Analysis using Npas4-deficient mice and adeno-associated virus revealed that Npas4 plays a role in suppressing cell death in infarct lesions and maintaining prognostic motor function. Npas4 expression was induced by abnormal Ca2+ influx into ischemic neurons. Npas4 reduces Ca2+ influx and facilitates cell survival after infarction. These results suggest that Npas4 acts as a negative regulator of Ca2+ influx in ischemic neurons.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

脳梗塞は発生頻度の高い疾患であり、多くの寝たきりを産んでいる。本研究の成果により、脳梗塞で発現が誘導される転写因子Npas4は、脳梗塞による細胞死を防ぐための、内在性の神経保護メカニズムに必須の因子であることが明らかとなった。今後、Npas4が虚血時のニューロンにおいて細胞死を防ぐメカニズムの詳細を明らかとすれば、その経路を人工的に活性化することも可能となり、新たな脳梗塞の治療や予防に繋がると期待される。