Treatment with Bifidobacteria can suppress Aβ accumulation and neuroinflammation in APP/PS1 mice

Qiong Wu; Qifa Li; Xuan Zhang; Michael Ntim; Xuefei Wu; Ming Li; Li Wang; Jie Zhao; Shao Li

doi:10.7717/peerj.10262

Treatment with Bifidobacteria can suppress Aβ accumulation and neuroinflammation in APP/PS1 mice

PeerJ. 2020 Oct 28:8:e10262. doi: 10.7717/peerj.10262. eCollection 2020.

Authors

Qiong Wu^#¹, Qifa Li^#², Xuan Zhang³, Michael Ntim¹, Xuefei Wu¹, Ming Li⁴, Li Wang⁵, Jie Zhao³, Shao Li¹

Affiliations

¹ Liaoning Provincial Key Laboratory of Cerebral Diseases in Department of Physiology, Dalian Medical University, Dalian, China.
² Functional Laboratory, Dalian Medical University, Dalian, China.
³ National-Local Joint Engineering Research Center for Drug-Research and Development (R & D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, China.
⁴ Department of Microecology, Dalian Medical University, Dalian, China.
⁵ College of Pharmacy, Dalian Medical University, Dalian, China.

^# Contributed equally.

Abstract

Background: Alzheimer's disease (AD), being a complex disorder, is affected either by genetic or environmental factors or both. It is observed that there is an excessive accumulation of amyloid β (Aβ) in the extracellular space of the brain. AD is the first neurodegenerative disease in the elderly, and so far there is no effective treatment. In recent years, many studies have reported that Alzheimer's disease has a relationship with gut microflora, indicating that regulating gut microbiota could offer therapeutic intervention for AD. This study explored the effect Bifidobacteria has in averting AD.

Methods: WT and APP/PS1 mice were used for the experiments. The mice were randomly assigned to four groups: WT group, WT + Bi group, AD group (APP/PS1 mouse) and AD + Bi group (Bifidobacteria-treated APP/PS1 mouse). Treatment with Bifidobacteria lasted for 6 months and mice were prepared for immunohistochemistry, immunofluorescence, Thioflavin S staining, Western blotting, PCR and Elisa quantitative assay.

Results: The results show that after 6 months of treatment with Bifidobacteria signiis to be lesficantly reduces Aβ deposition in cortex and hippocampus of AD mice. The level of insoluble Aβ in the hippocampus and cortex of AD+Bi mice was decreased compared with AD mice. Meanwhile, a significant decrease in the level of soluble Aβ in the cortex of AD+Bi mice but not in the hippocampus was observed. The activation of microglia and the release of inflammatory factors were also determined in this study. From the results, Bifidobacteria inhibited microglial activation and reduced IL-1β, TNF-α, IL-4, IL-6 and INF-γ release. Altogether, these results implied that Bifidobacteria can alleviate the pathological changes of AD through various effects.

Keywords: AD; Aβ; Bifidobacteria; Gut microflora.

Grants and funding

This work was supported by grants from the Liaoning Provincial Key R&D Program (2019020048-JH2/103), the Liaoning Revitalization Talents Program (XLYC1902044, XLYC1808031), the National Major Scientific and Technological Special Project for “Significant New Drugs Development” (2019zx09301102) and the National Natural Sciences Foundation of China (81571061, 81671061). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.