Age-associated gut microbiota impair hippocampus-dependent memory in a vagus-dependent manner.
JCI Insight
; 7(15)2022 08 08.
Article
in En
| MEDLINE
| ID: mdl-35737457
ABSTRACT
Aging is known to be associated with hippocampus-dependent memory decline, but the underlying causes of this age-related memory impairment remain highly debated. Here, we show that fecal microbiota transplantation (FMT) from aged, but not young, animal donors into young mice is sufficient to trigger profound hippocampal alterations, including astrogliosis, decreased adult neurogenesis, decreased novelty-induced neuronal activation, and impairment in hippocampus-dependent memory. Furthermore, similar alterations were reported when mice were subjected to an FMT from aged human donors. To decipher the mechanisms involved in mediating these microbiota-induced effects on brain function, we mapped the vagus nerve-related (VN-related) neuronal activity patterns and report that aged FMT animals showed a reduction in neuronal activity in the ascending-VN output brain structure, whether under basal condition or after VN stimulation. Targeted pharmacogenetic manipulation of VN-ascending neurons demonstrated that the decrease in vagal activity is detrimental to hippocampal functions. In contrast, increasing vagal ascending activity alleviated the adverse effects of aged mouse FMT on hippocampal functions and had a promnesic effect in aged mice. Thus, pharmacogenetic VN stimulation is a potential therapeutic strategy to lessen microbiota-dependent age-associated impairments in hippocampal functions.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gastrointestinal Microbiome
Type of study:
Risk_factors_studies
Limits:
Adult
/
Aged
/
Animals
/
Humans
Language:
En
Journal:
JCI Insight
Year:
2022
Type:
Article
Affiliation country:
France