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Evaluation of 5-hydroxytryptamine (5-HT) on Cognitive Function in Rats with Gut-Brain Axis Dysfunction Following
Yuqi Chen1,2, TianzhuTao1, Andong Zhao3
1Department of Anesthesiology, Air Force Medical Center, Beijing, China.
Molecular Neurobiology
|July 19, 2025
Summary
Acceleration stress impairs cognition by disrupting the gut-brain axis. Supplementing with 5-hydroxytryptamine (5-HT) reversed these cognitive deficits, rebalanced gut microbiota, and reduced neuroinflammation.
Area of Science:
- Neuroscience
- Gastroenterology
- Microbiology
Background:
- Acceleration stress, such as 10 Gz, can induce gut-brain axis dysfunction.
- This dysfunction is linked to cognitive impairments and neuroinflammation.
- The role of 5-hydroxytryptamine (5-HT) in modulating these effects is not fully understood.
Purpose of the Study:
- To investigate how 5-HT modulates acceleration-induced gut-brain axis dysfunction and cognitive impacts in rats.
- To explore the underlying microbiota-immune interactions and hippocampal neuroinflammation.
- To assess the therapeutic potential of 5-HT supplementation.
Main Methods:
- Rats were exposed to 10 Gz acceleration and supplemented with either 5-HT or a placebo.
- Cognitive function was assessed using the Morris water maze and open-field test.
- Serum cytokine levels, hippocampal microglial activation, and fecal microbiota composition were analyzed.
Main Results:
- 10 Gz exposure significantly impaired cognitive function and altered gut microbiota composition (increased Firmicutes/Bacteroidetes ratio).
- 5-HT supplementation reversed cognitive deficits, enhanced beneficial Lactobacillus abundance, and attenuated serum TNF-α and IL-1β levels.
- Acceleration stress induced hippocampal CA1 microglial activation, which was significantly reduced by 5-HT supplementation.
Conclusions:
- 5-HT plays a crucial role in mitigating acceleration-induced cognitive deficits.
- Supplementation with 5-HT ameliorates these deficits by rebalancing gut microbiota and suppressing hippocampal neuroinflammation.
- These findings suggest 5-HT as a potential therapeutic target for gut-brain axis disorders.

