Action Mechanism of probiotics effective in preventing the onset of intractable dementia and brain-gut correlation.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06425
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Obihiro University of Agriculture and Veterinary Medicine
• Principal Investigator: Ishii Toshiaki 帯広畜産大学, 畜産学部, 教授 (50264809)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: B. breve A1 [MCC1274] / MPTP / パーキンソン病 / 難治生認知障害 / 記憶消去 / 脳-腸-微生物相関 / 海馬 / neuropsin

Outline of Final Research Achievements

We generated a mouse model of Parkinson's disease (PD mice) by intraperitoneal injection of MPTP, which destroys DA neurons in the substantia nigra of the midbrain, and B. breve A1 restored the abnormal hyper- extinction of hippocampal memory exhibited by PD mice to normal levels. B. breve A1 restored neuropsin mRNA and protein expression in the hippocampus of PD mice, resulting in normalizing synaptic protein expression and spine density on dendrites in the CA1 region and in possibly normalizing attenuation of inhibitory GABAergic neurotransmission. Our findings also suggest that the cranial normalizing neural mechanism of B. breve A1 is partially mediated by the activation of integrin-linked kinase and its downstream Akt in hippocampal neurons.

Free Research Field

神経科学、神経薬理学

Academic Significance and Societal Importance of the Research Achievements

PDの認知症の発症を予防するプロバイオティクスの検索過程でその有効性を認めたBifidobacterium breve strain A1 [MCC1274] (B. breve A1)の作用機構を解明し、PDの難治性認知障害に対して安全性の高い治療あるいは予防に向けたプロバイオティクス有効活用による機能性食品開発の手がかりを見出すことが出来た。また、B. breve A1はGABA-A受容体拮抗薬による不随意運動の亢進を回復させたことから(特願2022-089546 抗てんかん用組成物 [発明者：石井利明])、B. breve A1はてんかん発作の予防にも有効である可能性が示唆された。