# GABA-Induced Exosomes Improve Memory Impairment in Aged Mice

## TL;DR

GABA improves memory in aged mice by boosting exosome activity linked to brain health and reducing aging signs.

## Contribution

Demonstrates that GABA improves memory via exosome-mediated neuronal and mitochondrial activation in aged mice.

## Key findings

- GABA-treated mice showed improved memory and discrimination index scores.
- GABA-induced exosomes promoted neurite outgrowth and reduced neuroinflammation.
- GABA enhanced exosomal miRNA expression linked to neuronal activation and anti-senescence.

## Abstract

Gamma-aminobutyric acid (GABA) has been implicated in gut–brain interactions and neuronal activation. We hypothesized that GABA could ameliorate memory decline. We investigated whether oral GABA administration ameliorated age-related cognitive decline in aged mice (C57BL/6J, male) and explored the role of circulating exosomes in mediating these effects. Aged mice that drank water containing 0.5% GABA exhibited significantly improved discrimination index scores compared with that of controls, indicating enhanced memory function. Their plasma-derived exosomes induced neurite outgrowth and mitochondrial activation and restored neuronal activity in SH-SY5Y cells. GABA enhanced the exosomal expression of several miRNAs linked to neuronal activation, longevity, and anti-senescence pathways. Plasma-derived exosomes also restored object recognition memory, reduced hippocampal neuroinflammation, and decreased senescent cell markers (p21 and γH2AX) in aged mice. Additionally, mitochondria- and neurite-related genes were upregulated, and pathways associated with oxidative phosphorylation and Alzheimer’s disease were enriched. Collectively, long-term GABA administration was found to improve cognitive function of aged mice through the secretion of functional exosomes.