Pathological mechanisms and therapeutic strategies for elderly-onset epilepsy by targeting senescent brain pericytes

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16065
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Fukuoka University
• Principal Investigator: Iwao Takuro 福岡大学, 薬学部, 助教 (30846374)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 血液脳関門 / 高齢発症てんかん / ペリサイト / ドコサヘキサエン酸

Outline of Final Research Achievements

In this study, we aimed to elucidate the pathological mechanisms of elderly-onset epilepsy and examined therapeutic effect of docosahexaenoic acid (DHA). We revealed that pericytes, which are the component of Blood-Brain barrier (BBB) and play a key role in maintaining BBB integrity, are reduced and underwent cellular senescence during aging. The changes in pericytes are probably involved in decreased DHA transport across the BBB, the BBB disruption, and the formation of neuroinflammation with aging. Furthermore, we showed that the seizure sensitivity was increased with the age-related BBB disruption and neuroinflammation. These age-related pathological processes were improved by a long-term dietary DHA supplementation.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

本研究結果は、未だ明確な病態形成機構が明らかになっていない高齢発症てんかんにおいて、老化ペリサイトを基軸とした潜在的な病態形成機構を明らかにした点に学術的意義がある。また、DHA摂取による血液脳関門の保護が加齢に伴う脳内炎症の拡大及びてんかん感受性の増大を抑制することを明らかにし、DHAの補充が高齢者において発症率の高いてんかんの発症予防や治療に応用できる可能性を提示した点に社会的意義がある。これは「血管を治療し神経を護る」という新たな治療戦略の構築に資するものである。