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  2. Transplantation of fecal microbiota from APP/PS1 mice and Alzheimer's disease patients enhanced endoplasmic reticulum stress in the cerebral cortex of wild-type mice

Transplantation of fecal microbiota from APP/PS1 mice and Alzheimer's disease patients enhanced endoplasmic reticulum stress in the cerebral cortex of wild-type mice

  • Front Aging Neurosci. 2022 Jul 28;14:858130. doi: 10.3389/fnagi.2022.858130.
Fang Wang 1 Yongzhe Gu 2 Chenhaoyi Xu 2 Kangshuai Du 3 Chence Zhao 4 Yanxin Zhao 2 Xueyuan Liu 1 2
Affiliations

Affiliations

  • 1 School of Clinical Medicine, Weifang Medical University, Weifang, China.
  • 2 Department of Neurology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
  • 3 Shanghai Clinical College, Anhui Medical University, Hefei, China.
  • 4 School of Nursing, Medical College, Soochow University, Suzhou, China.
Abstract

Background and purpose: The gut-brain axis is bidirectional and the imbalance of the gut microbiota usually coexists with brain diseases, including Alzheimer's disease (AD). Accumulating evidence indicates that endoplasmic reticulum (ER) stress is a core lesion in AD and persistent ER stress promotes AD pathology and impairs cognition. However, whether the imbalance of the gut microbiota is involved in triggering the ER stress in the brain remains unknown.

Materials and methods: In the present study, fecal microbiota transplantation (FMT) was performed with gut microbiota from AD patients and APP/PS1 mice, respectively, resulting in two mouse models with dysregulated gut microbiota. The ER stress marker protein levels in the cerebral cortex were assessed using western blotting. The composition of the gut microbiota was assessed using 16S rRNA sequencing.

Results: Excessive ER stress was induced in the cerebral cortex of mice after FMT. Elevated ER stress marker proteins (p-perk/PERK, p-eIF2α/eIF2α) were observed, which were rescued by 3,3-dimethyl-1-butanol (DMB). Notably, DMB is a compound that significantly attenuates serum trimethylamine-N-oxide (TMAO), a metabolite of the gut microbiota widely reported to affect cognition.

Conclusion: The findings indicate that imbalance of the gut microbiota induces ER stress in the cerebral cortex, which may be mediated by TMAO.

Keywords

Alzheimer’s disease; ER stress; FMT; TMAO; gut microbiota.

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