Elucidation of drug-induced extrapyramidal symptoms caused by abnormalities in endocytosis of astrocytes

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06610
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Himeji Dokkyo University
• Principal Investigator: Yamamoto Naoki 姫路獨協大学, 薬学部, 教授 (90393157)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 錐体外路障害 / エンドサイトーシス / オートファジー / アストロサイト

Outline of Final Research Achievements

This study focused on drug-induced extrapyramidal symptoms (DI-EPS), one of the side effects that increases with polypharmacy in elderly people. Using various drugs that induce DI-EPS, we clarify the causal relationship between endocytosis abnormalities in primary cultured astrocytes and DI-EPS. Donepezil, a drug for Alzheimer's disease, was confirmed to cause specific morphological changes in astrocytes as well as abnormal endocytosis via σ1 receptors. The effects of donepezil were suppressed by σ1 receptor agonists. Similar results to those of haloperidol and donepezil were obtained when other drugs that induce DI-EPS were used.

Free Research Field

神経化学

Academic Significance and Societal Importance of the Research Achievements

古くから副作用にDI-EPSを誘発することが知られている薬剤が、アストロサイトに特異な形態変化をもたらし、エンドサイトーシス異常を誘発することを以前に明らかにし報告している。アストロサイトのエンドサイトーシス異常に伴う代謝異常が、神経細胞機能抑制を誘発する可能性は高い。また、その影響を検討することは、学術的に非常に意義があるものと考える。