Effect of periodontitis on blood-brain barrier related genes and its relation to Alzheimer's disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K24078
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Health Sciences University of Hokkaido
• Principal Investigator: MORIKAWA Tetsuro 北海道医療大学, 歯学部, 助教 (90845463)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 血液脳関門 / LPS / 歯周病

Outline of Final Research Achievements

It has been suggested that periodontal disease may have a role in pathogenesis of Alzheimer's disease. In this study, we investigated the effect of Porphyromonas gingivalis, one of the periodontal pathogens, on the blood-brain barrier. Human Brain Microvascular Endothelial cells were cultured in a vascular endothelial medium for 24 hours and P. gingivalis derived Lipopolysaccharide (LPS) was added to the cells at a concentration of 1.0 ug / ml, The tight junction related genes such as Claudin-1,-3,-5,-12, Occludin, ZO-1 and VE-cadherin were analyzed for changes in mRNA expression level using qRT-PCR. The results showed that the mRNA level of Claudin-5 was significantly downregulated in cells cultured with LPS as compared to control.

Free Research Field

口腔病理

Academic Significance and Societal Importance of the Research Achievements

脳には血液脳関門（BBB）があり、血液中から脳組織への物質の移行は厳密に制限されている。BBBは脳毛細血管内皮細胞が密接に結合し、その周囲に脳血管周皮細胞とペリサイトが存在する。これまで、この3種類のBBB構成細胞の機能についての研究は進められてきたが、歯周病原菌がBBB構成細胞にどのように影響するかについては仮説の域を出ていないのが現状である。そこで本研究では、LPSがBBBに対してどのような機序で障害を及ぼし、脳海馬へ影響するかについて検証する。これらの機序が明らかとなれば、P. gingivalisによるアルツハイマー病発症・進行の病態解明が大きく前進するものと考えられる。