Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
Trimethylamine-N-oxide promotes brain aging and cognitive impairment in mice
First author：Li Dang,Ke Yilang
Corresponding author：Zheng Lemin,Hong Huashan
essential_information
- Person in charge：Li Dang,Ke Yilang
- Data Sources： OTHERS
- Number of papers：OTHERS20190613
- Published time：2018-08-01
2018-08-01
Published articles
Journal：Aging Cell
Publication type: Original Article
IF(IF): 9.304
PMID: 29749694 Link To Pubmed Full text Download
Background And Purpose
Method
To explore the relationship between TMAO and brain aging, we analysed the plasma levels of TMAO in both humans and mice and administered exogenous TMAO to 24-week-old senescence-accelerated prone mouse strain 8 (SAMP8) and age-matched senescence-accelerated mouse resistant 1 (SAMR1) mice for 16 weeks.
Conclusion
Our findings suggested that TMAO could induce brain aging and age-related cognitive dysfunction in SAMR1 mice and aggravate the cerebral aging process of SAMP8 mice, which might provide new insight into the effects of intestinal microbiota on the brain aging process and help to delay senescence by regulating intestinal flora metabolites.
Main results
We found that the plasma levels of TMAO increased in both the elderly and the aged mice. Compared with SAMR1-control mice, SAMP8-control mice exhibited a brain aging phenotype characterized by more senescent cells in the hippocampal CA3 region and cognitive dysfunction. Surprisingly, TMAO treatment increased the number of senescent cells, which were primarily neurons, and enhanced the mitochondrial impairments and superoxide production. Moreover, we observed that TMAO treatment increased synaptic damage and reduced the expression levels of synaptic plasticity-related proteins by inhibiting the mTOR signalling pathway, which induces and aggravates aging-related cognitive dysfunction in SAMR1 and SAMP8 mice, respectively.