期刊
FRONTIERS IN NEUROSCIENCE
卷 16, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2022.939915
关键词
apolipoprotein E; aging; cognitive function; gut microbiota; metabolomics; oxidative stress
资金
- Hunan Provincial Department of Education Open Platform Fund
- Hunan Provincial Traditional Chinese Medicine Research Project
- Changsha Natural Science Foundation
- Hunan University of Chinese Medicine Double First-Class Discipline Open Fund
- [20K096]
- [2020098]
- [kq2014223]
- [2022ZYX15]
This study investigated the role of ApoE in cognitive function in aging mice through the gut microbiota-brain axis. The results showed that ApoE deletion exacerbated cognitive dysfunction, hippocampal synaptic ultrastructural damage, and dysregulation of synaptic proteins. It also altered the gut microbial makeup and hippocampal metabolic profile.
The gut microbiota plays an important role in central nervous system (CNS) disorders. Apolipoprotein E (ApoE) can affect the composition of the gut microbiota and is closely related to the CNS. However, the mechanism by which ApoE affects cognitive dysfunction through the gut microbiota-brain axis has thus far not been investigated. In this study, we used wild-type mice and ApoE knockout (ApoE(-/-)) mice to replicate the aging model and examined the effects of ApoE deletion on cognitive function, hippocampal ultrastructure, synaptophysin (SYP) and postsynaptic density 95 (PSD-95) in aging mice. We also explored whether ApoE deletion affects the gut microbiota and the metabolite profile of the hippocampus in aging mice and finally examined the effect of ApoE deletion on lipids and oxidative stress in aging mice. The results showed that the deletion of ApoE aggravated cognitive dysfunction, hippocampal synaptic ultrastructural damage and dysregulation of SYP and PSD-95 expression in aging mice. Furthermore, ApoE deletion reduced gut microbial makeup in aging mice. Further studies showed that ApoE deletion altered the hippocampal metabolic profile and aggravated dyslipidemia and oxidative stress in aging mice. In brief, our findings suggest that loss of ApoE alters the composition of the gut microbiota, which in turn may affect cognitive function in aging mice through the gut microbiota-brain axis.
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