Impaired Cognitive Function Following Chronic Diazepam Treatment in Middle-Aged Mice

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18234
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Hirosaki University
• Principal Investigator: Furukawa Tomonori 弘前大学, 医学研究科, 助教 (60402369)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ベンゾジアゼピン / ジアゼパム / 認知機能 / 海馬LTP / 運動

Outline of Final Research Achievements

It has been reported that long-term benzodiazepine administration induces cognitive decline in older adults, which provides evidence for toxicity. In this study, we investigated the mechanism of cognitive decline due to long-term use of diazepam, a benzodiazepine, and the preventive effect of exercise for the adverse effect of diazepam. In hippocampal region of chronically diazepam administered middle-aged mice, we analyzed apoptosis, neurogenesis, morphological changes in pyramidal neurons and neural circuit function. There were no effects of chronic diazepam on cell death or neurogenesis, but spine density of pyramidal neurons was decreased and long-term potentiation of CA1 and CA3 were attenuated by both diazepam administration and aging. Furthermore, it was found that the adverse effects of diazepam can be prevented by long-term exercise by force-running wheel.

Free Research Field

神経生理学

Academic Significance and Societal Importance of the Research Achievements

本研究結果は、長期的なジアゼパム使用によって生じる認知機能低下が海馬領域における神経細胞の新生や細胞死ではなく、形態的特徴の変化による機能的減退によって引き起こされることを示唆するものであり、ジアゼパムの中枢神経系における詳細な分子的作用機序解明への発展が期待できる。運動による認知機能向上は以前から注目されており、近年、末梢血中の運動由来分子が同定され、詳細な研究が期待されている。本研究成果は、運動由来分子の中枢における機能的特性の解明に貢献できると考えられる。運動由来分子の機能的特性が明らかになれば、ジアゼパム等による認知機能減退の予防法や治療法への発展が期待できる。