Association of mental disorder and decrease of Npas4

2017 Fiscal Year Final Research Report

• Project/Area Number: 26460095
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Nagoya University
• Principal Investigator: HIBI YOKO 名古屋大学, 医学部附属病院, 薬剤師 (70295616)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: Neuronal PAS domain 4 / 遺伝子欠損マウス / 精神疾患 / 脳

Outline of Final Research Achievements

Neuronal PAS domain 4 (NPAS4) has recently been shown to regulate the development of GABAergic inhibitory synapses. We previously reported that Npas4 mRNA expression levels were reduced in the hippocampus of mice exposed to social isolation or restraint stress. In the present study, we suggested that restraint stress increase the DNA methylation level of Npas4 promoter region. We analyzed the effect of decrease of Npas4 expression on the function of GABA neurons. Npas4-knockout mice were impaired in pre-pulse inhibition. GABA receptors were decreased in the cerebellum of Npas4-knockout mice. The expression level of Npas4 mRNA was significantly increased after the pentylenetetrazol (PTZ) treatment. Npas4 increased Homer1a promoter activity. Npas4 function as a molecular switch to initiate homeostatic scaling and the targetinc of Npas4-Homer1a signaling may provide new approaches for the treatment of epilepsy.

Free Research Field

神経科学　行動薬理