Marked Response of Rat Ileal and Colonic Microbiota After the Establishment of Alzheimer's Disease Model With Bilateral Intraventricular Injection of Aβ (1-42).

Qing Xu,Yanjun Liu,Qiaozhi Yin,Xiaoqin Zhao,Yuqing Fan,Yunhui Chen,Chang Chen,Guihua Wei,Chunxiao Xiang,Lingmiao Wen,Tinglan Zhang,Tian-E Zhang,Wei Xiong,Chunlan Chen,Zhiyong Yan

doi:10.3389/fmicb.2022.819523

Abstract

Alzheimer’s disease (AD) is a common neurodegenerative disease. More evidence has shown that gut microbiota is closely associated with AD. Also, studies have shown that the distribution of gut microbiota vary in different sections of the intestine. In this study, a rat model of AD was established using a bilateral intraventricular injection of β-amyloid (1-42) [Aβ (1-42)], and the behavior of rats, hippocampal Aβ (1-42) deposition, and the ileal and colonic microbiota in each group were analyzed. We observed that the model rats had obvious memory and cognitive impairment, increased Aβ (1-42) deposition, indicating that the AD model was successfully established. Through 16S rRNA-sequencing analysis, we found that α diversity, β diversity, and dominant microbiota in the ileum and colon of normal rats were significantly different, showing spatial heterogeneity. Additionally, the surgery and injection of Aβ (1-42) caused various degrees of disturbances in the ileal and colonic microbiota of rats. These findings provide new insights for the study of the gut microbiota of AD rats and help advance the development of therapeutic strategies for intervening AD through the gut microbiota.

Highlights

Alzheimer’s disease (AD) is an age-related neurodegenerative disease
It was observed that the injection of Aβ (1-42) caused damage to the memory and cognitive function of rats, but it was not affected by the surgery
The behavioral results of this study showed significant changes in the water maze experiment in the model group rats compared with the normal and sham-operated groups, which indicates that bilateral ventricular injection of Aβ (1-42) impaired memory and cognitive functions in rats and successfully established the rat model of AD

Summary

Introduction

Alzheimer’s disease (AD) is an age-related neurodegenerative disease. Its main characteristics are β-amyloid deposition and neurofibrillary tangles, and its clinical manifestations begin with slight memory decline and can eventually develop into severe self-care and cognitive impairment (Mathys et al, 2019; Kim et al, 2020). According to the Alzheimer’s Disease International (2016), the number. Gut Microbiota in AD Rats of people with dementia in the world is about 50 million (Alzheimer’s Disease International, 2016). We established an AD model by bilateral intraventricular injection of Aβ (1-42) based on the β-amyloid cascade hypothesis. This method has been widely used (Yang et al, 2018; Xu et al, 2019), and many studies have shown that Aβ (1-42) injection can cause memory impairment and changes Brain Derived Neurotrophic Factor (BDNF) or 5hydroxytryptamine(2A)[5-HT(2A)] receptor levels in the serum and brain (O’Hare et al, 1999; Christensen et al, 2008)

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