How anti-Alzheimer's drug affect microglia and neurovascular unit ?

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10275
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Saga University
• Principal Investigator: Mizoguchi Yoshito 佐賀大学, 医学部, 准教授 (60467892)
• Co-Investigator(Kenkyū-buntansha): 門司 晃 佐賀大学, 医学部, 教授 (00294942)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ミクログリア / アルツハイマー型認知症 / 認知症治療薬 / ドネペジル / カルシウム / 貪食能

Outline of Final Research Achievements

Microglia are resident innate immune cells which release many factors including proinflammatory cytokines when they are activated. As one of underlying mechanisms of Alzheimer's disease (AD), dysregulation of intracellular Ca2+ homeostasis has also been proposed as a common cause of neural dysfunction. Donepezil, one of acetylcholinesterase (AChE) inhibitors, is clinically used for the treatment of AD. The major mechanism of donepezil’s effects is to inhibit neuronal AChE activity. We examined whether pretreatment with donepezil affects the intracellular Ca2+ mobilization and phagocytic activity in rodent microglial cells. We observed that pretreatment with donepezil promoted phagocytic activity of mouse primary microglial cells.These suggest that donepezil could directly modulate the microglial function in vitro and might favor the shift of microglial cells from a pro-inflammatory to a more neuroprotective phenotype in the rodent brain.

Free Research Field

精神薬理学

Academic Significance and Societal Importance of the Research Achievements

高齢化社会は今後も続き多数の認知症高齢者に認知症治療薬が処方されていくと考えられるが認知症治療薬がニューロン以外の細胞に及ぼす作用および細胞内メカニズムについて驚くほど知見が不足しているのが現状である。本研究課題の遂行によりニューロンーグリアー脳血管系の老化を背景とした認知症の病態解明および治療薬開発に繋がる新たな知見を得られる可能性が高いと考える。