Related Experiment Video
Updated: Sep 6, 2025
Intracerebroventricular Delivery of Gut-Derived Microbial Metabolites in Freely Moving Mice
Published on: June 2, 2022
Age-associated gut microbiota impair hippocampus-dependent memory in a vagus-dependent manner
Damien Rei1, Soham Saha1, Marianne Haddad1
1Institut Pasteur de Paris, Paris Cité University, CNRS UMR 3571, Perception and Memory Unit, Paris, France.
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.
Insights
Fecal microbiota transplantation from aged donors impairs hippocampal memory in young mice by altering vagus nerve activity. Stimulating the vagus nerve may counteract these age-related memory deficits.
Area of Science:
- Neuroscience
- Gastroenterology
- Aging Research
Background:
- Aging is linked to memory decline, particularly hippocampus-dependent memory.
- The exact causes of age-related memory impairment are still debated.
- The gut microbiome's role in brain aging is an emerging area of research.
Purpose of the Study:
- To investigate the impact of fecal microbiota transplantation (FMT) from aged donors on hippocampal function in young mice.
- To explore the underlying mechanisms, focusing on vagus nerve (VN) activity.
- To assess the therapeutic potential of modulating VN activity for age-associated memory impairment.
Main Methods:
- Fecal microbiota transplantation (FMT) from aged and young mice (and humans) into young mice.
- Assessment of hippocampal alterations (astrogliosis, neurogenesis, neuronal activation).
- Mapping of vagus nerve-related (VN-related) neuronal activity and targeted pharmacogenetic manipulation of VN-ascending neurons.
Main Results:
- Aged FMT induced hippocampal alterations and memory deficits in young mice, mirroring effects seen with aged human FMT.
- Reduced neuronal activity in ascending-VN output structures was observed in aged FMT mice.
- Decreased vagal activity worsened hippocampal function, while increased activity alleviated aged FMT effects and improved memory in aged mice.
Conclusions:
- The gut microbiome significantly influences brain aging and hippocampal function.
- Vagus nerve activity is a critical mediator of microbiota-induced effects on the hippocampus.
- Pharmacogenetic stimulation of the vagus nerve presents a potential therapeutic strategy for microbiota-dependent age-associated memory decline.
