Disrupted gut microbiota aggravates working memory dysfunction induced by high-altitude exposure in mice

Area of Science:

• Neuroscience
• Microbiology
• Altitude Physiology

Background:

• The microbiome-gut-brain axis (MGBA) is crucial for understanding high-altitude effects on the brain.
• Limited research exists on high-altitude exposure's impact on the MGBA and cognitive function.
• Mechanisms linking high-altitude exposure, gut microbiota, and brain function require further elucidation.

Purpose of the Study:

• To investigate if high-altitude-induced working memory dysfunction is exacerbated by gut microbiota disruption.
• To explore the relationship between high-altitude exposure, gut microbiota alterations, and cognitive performance.
• To provide insights into the MGBA in the context of environmental stress.

Main Methods:

• C57BL/6 mice were exposed to simulated high altitude (3,500-4,000m) for 14 days.
• One group received antibiotic treatment to disrupt gut microbiota (HAE-A).
• Working memory was assessed using novel object recognition and P300 event-related potentials; gut microbiota composition and prefrontal cortex biochemistry were analyzed.

Main Results:

• Antibiotic treatment aggravated high-altitude-induced working memory dysfunction.
• Disturbed gut microbiota negatively impacted antioxidant capacity (T-AOC, MDA, SOD, GSH-Px) and apoptosis markers (bcl-2, Bax, caspase-3) in the prefrontal cortex.
• High-altitude and antibiotic treatment altered colonic microbiota richness, diversity, and composition, with specific taxa like S24-7, Lachnospiraceae, and Lactobacillaceae showing significant changes.

Conclusions:

• Disrupted gut microbiota exacerbates working memory dysfunction in mice exposed to high altitude.
• This study supports a connection between high-altitude exposure and the microbiome-gut-brain axis.
• Gut microbiota modulation may be a target for mitigating cognitive impairments associated with high-altitude environments.