北海道支部について

Molecular Pathogenesis of Alzheimer’s Disease: Impact of the 
Microbiome on Amyloid Deposition and Neuroinflammation

Sangram Sisodia　博士 

Department of Neurobiology, University of Chicago, Chicago Il USA

令和元年10月24日(木)　17:00〜18:30  

北海道大学薬学部1階　臨床薬学講義室（１階正面玄関突き当たり）

北海道大学大学院薬学研究院　日本生化学会北海道支部

Objectives: Animal models of Alzheimer’s disease (AD) recapitulate the severe amyloidosis and neuroinflammation that is evident in the human disease. Neuroinflammation is associated with activation of astrocytes and microglia in response to injury, but the role of peripheral tissues and more importantly, the microbiota in regulating innate immunity that in turn leads to CNS dysfunction has not been defined. We have tested the hypothesis that the composition of the intestinal microbiome plays a role in modulating neuro-inflammation that will ultimately influence amyloid deposition in two established mouse models of Ab-amyloidosis.

Methods: We orally administered a combination of antibiotics to induce rapid and sustained alterations in gut microbial populations. The antibiotic cocktail was administered either postnatally or throughout the lifetime of the animal prior to cull and we employed IHC, biochemical and transcriptomic assays to evaluate amyloid deposition and neuroinflammation in the mouse models. 

Results:  Our studies indicate that alterations in the microbiome parallel changes in plasma cytokines and chemokines, reductions in amyloid deposition and modulation of morphological and transcriptional landscapes of microglia that only occurs in male, but not female animals.

Conclusions:  Our studies reveal an unexpected, but significant alteration in amyloid deposition and microglial phenotypes in the brains of transgenic mice upon treatment with orally administered antibiotics.

北海道大学大学院薬学研究院　神経科学研究室
  鈴木利治
  (TEL: 011-706-3250　tsuzuki@pharm.hokudai.ac.jp)