Elucidation of the mechanism of delirium onset caused by dysfunction of the stress-sensitive factor NPAS4 and development of therapeutic drugs

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07181
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Nagoya City University
• Principal Investigator: HIBI YOKO 名古屋市立大学, 医薬学総合研究院(医学), 教授 (70295616)
• Co-Investigator(Kenkyū-buntansha): 木村 和哲 名古屋市立大学, 医薬学総合研究院(医学), 教授 (00423848) ; 片岡 智哉 千葉科学大学, 薬学部, 准教授 (20737928) ; 堀田 祐志 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (90637563)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: Npas4 / せん妄

Outline of Final Research Achievements

NPAS4 is a transcription factor thought to be the key to the relationship between stress, GABAergic nervous system disorders, and the onset of psychiatric symptoms. In this study, we have approached this issue from both the basic analysis and the analysis of delirium onset using clinical data. In the basic analysis, we have focused on the analysis of compounds that induce Npas4 expression using cells and animals, as well as the brain-kidney crosstalk. In the field of clinical research, we focused on the possibility that NPAS4 may affect the relationship between benzodiazepine drugs and the onset of delirium, and investigated medical records regarding risk factors for delirium and drugs used. We investigated the effects of the combined use of opioids and benzodiazepine drugs in patients, but no clear trends were found.

Free Research Field

臨床薬理学

Academic Significance and Societal Importance of the Research Achievements

せん妄は周術期や炎症性疾患や薬剤が誘発因子となって起こる精神神経疾患であり、脳の器質的障害もリスク因子である。本研究は、神経発達に関わりストレスで発現抑制する転写因子NPAS4とせん妄の関連を調べることを目的とした。研究期間に十分な成果を出すことはできなかったが、オピオイドとベンゾジアゼピン系薬剤を使用する患者のせん妄発現の調査を行い、また、末梢神経障害による排尿障害や、抗がん剤や抗菌薬による薬剤性急性腎障害とせん妄発現の関連などの臨床現場で重要なテーマへ、Npas4研究の視野を広げて取り組んでいく基盤を作ることができた。