Ketogenic Diet Mitigates Age-Related Cognitive Decline and Neuroinflammation in Rats, While Antibiotics Exacerbate...

Area of Science:

• Neuroscience
• Metabolic research
• Aging research

Background:

• The ketogenic diet (KD), a high-fat, low-carbohydrate diet, shows neuroprotective potential.
• Aging is associated with cognitive decline and increased neuroinflammation.
• The gut microbiota's role in brain health and aging is increasingly recognized.

Purpose of the Study:

• To investigate the effects of KD alone and combined with antibiotic-induced gut microbiota depletion on cognition and neuroinflammation in aging rats.
• To determine if KD can mitigate age-related cognitive deficits and neuroinflammation, independent of gut microbiota status.

Main Methods:

• Thirty-two aged male rats were divided into four groups: control diet (CD), KD, antibiotics with CD (AB), and antibiotics with KD (KDAB).
• Diets were administered for 10 weeks, with antibiotics administered during the final week.
• Cognitive function was assessed using the Morris Water Maze and Novel Object Recognition Test.
• Hippocampal and prefrontal cortex levels of BDNF and inflammatory cytokines (TNF-α, IL-1β, IL-10) were measured.

Main Results:

• Ketogenic diet groups (KD and KDAB) showed increased β-hydroxybutyrate and reduced glucose levels.
• Both KD groups exhibited enhanced cognitive performance, elevated BDNF and IL-10, and reduced TNF-α and IL-1β compared to non-KD groups.
• Antibiotic treatment alone caused transient spatial memory impairment but reduced TNF-α.
• The ketogenic diet improved cognition and neuroprotection irrespective of microbiota status.

Conclusions:

• The ketogenic diet demonstrates significant neuroprotective effects in aging rats, enhancing cognitive function and reducing neuroinflammation.
• These benefits are observed even when the gut microbiota is disrupted by antibiotics.
• The ketogenic diet may be a viable strategy to promote brain resilience and combat cognitive decline during aging.