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High Salt Elicits Brain Inflammation and Cognitive Dysfunction, Accompanied by Alternations in the Gut Microbiota and Decreased SCFA Production
- Source :
- Journal of Alzheimer's disease : JAD. 77(2)
- Publication Year :
- 2020
-
Abstract
- Background: Excessive salt intake is considered as an important risk factor for cognitive impairment, which might be the consequence of imbalanced intestinal homeostasis. Objective: To investigate the effects of dietary salt on the gut microbiota and cognitive performance and the underlying mechanisms. Methods: Adult female C57BL/6 mice were maintained on either normal chow (control group, CON) or sodium-rich chow containing 8% NaCl (high-salt diet, HSD) for 8 weeks. Spatial learning and memory ability, short-chain fatty acids (SCFAs) concentrations, gut bacterial flora composition, blood-brain barrier permeability, and proinflammatory cytokine levels and apoptosis in the brain were evaluated. Results: The mice fed a HSD for 8 weeks displayed impaired learning and memory abilities. HSD significantly reduced the proportions of Bacteroidetes (S24-7 and Alloprevotella) and Proteobacteria and increased that of Firmicutes (Lachnospiraceae and Ruminococcaceae). SCFA concentrations decreased in the absolute concentrations of acetate, propionate, and butyrate in the fecal samples from the HSD-fed mice. The HSD induced both BBB dysfunction and microglial activation in the mouse brain, and increased the IL-1β, IL-6, and TNF-α expression levels in the cortex. More importantly, the degree of apoptosis was higher in the cortex and hippocampus region of mice fed the HSD, and this effect was accompanied by significantly higher expression of cleaved caspase-3, caspase-3, and caspase-1. Conclusion: The HSD directly causes cognitive dysfunction in mice by eliciting an inflammatory environment and triggering apoptosis in the brain, and these effects are accompanied by gut dysbiosis, particularly reduced SCFA production.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Hippocampus
Inflammation
Butyrate
Gut flora
Blood–brain barrier
Proinflammatory cytokine
03 medical and health sciences
Mice
0302 clinical medicine
Internal medicine
medicine
Animals
Cognitive Dysfunction
Salt intake
Sodium Chloride, Dietary
Maze Learning
biology
Chemistry
General Neuroscience
Lachnospiraceae
Brain
General Medicine
biology.organism_classification
Fatty Acids, Volatile
Gastrointestinal Microbiome
Mice, Inbred C57BL
Psychiatry and Mental health
Clinical Psychology
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Blood-Brain Barrier
Female
Geriatrics and Gerontology
medicine.symptom
Inflammation Mediators
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 18758908
- Volume :
- 77
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of Alzheimer's disease : JAD
- Accession number :
- edsair.doi.dedup.....2e8850c12ede3990fd27d29167732e3f