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SCFAs Ameliorate Chronic Postsurgical Pain-Related Cognition Dysfunction via the ACSS2-HDAC2 Axis in Rats
Zhen Li1, Tianning Sun1, Zhigang He1
1Department of Anesthesiology and Pain Medicine, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Molecular Neurobiology
|July 28, 2022
Summary
Chronic postsurgical pain in rats is linked to cognitive deficits and altered gut bacteria producing short-chain fatty acids (SCFAs). SCFA supplementation improved cognition by modulating brain pathways.
Area of Science:
- Neuroscience
- Microbiology
- Gastroenterology
Background:
- Chronic postsurgical pain (CPSP) often co-occurs with cognitive impairments.
- Gut microbial metabolites, particularly short-chain fatty acids (SCFAs), are increasingly recognized for their role in cognitive function regulation.
- The precise mechanisms linking CPSP, gut microbiota, and cognitive deficits remain largely unexplored.
Purpose of the Study:
- To investigate the relationship between gut microbiota composition, SCFA production, and cognitive deficits in a rat model of CPSP.
- To explore the therapeutic potential of SCFAs in ameliorating pain-related cognitive dysfunction.
- To elucidate the molecular mechanisms underlying SCFA-mediated cognitive improvement in the brain.
Main Methods:
- Hierarchical clustering and 16S rRNA gene sequencing to analyze gut microbiota composition in CPSP rats.
- Fecal microbiota transplantation (FMT) to establish causal links between microbial alterations and cognitive behavior.
- Administration of SCFAs to assess their effects on cognitive deficits and molecular markers in brain regions.
Main Results:
- Over two-thirds of CPSP rats exhibited cognitive impairment, associated with aberrant SCFA-producing gut bacteria.
- FMT from cognitively impaired rats to healthy recipients induced cognitive deficits, confirming a causal microbial link.
- SCFA treatment significantly alleviated cognitive-behavioral deficits in CPSP rats.
- SCFA supplementation normalized histone acetylation and synaptic transmission in the medial prefrontal cortex, hippocampus, and amygdala via the ACSS2-HDAC2 axis.
Conclusions:
- Gut microbiota dysbiosis and reduced SCFA production contribute to cognitive dysfunction in CPSP.
- SCFAs represent a promising therapeutic target for managing pain-associated cognitive deficits.
- The ACSS2-HDAC2 pathway in key brain regions is a critical mediator of SCFA effects on cognition.
