Calorie Restriction Attenuates Memory Impairment and Reduces Neuroinflammation in Obese Aged Rats

Area of Science:

• Neuroscience
• Gerontology
• Nutritional Science

Background:

• Obesity and aging exacerbate central nervous system inflammation.
• Managing obesity in aging populations presents unique challenges.
• Caloric restriction (CR) is known for its broad health benefits.

Purpose of the Study:

• To investigate if CR can mitigate obesity-related brain alterations and cognitive decline in aged rats.
• To explore the effects of CR on neuroinflammation and hippocampal function in the context of aging and obesity.

Main Methods:

• 18-month-old male rats were fed a cafeteria diet to induce obesity.
• Cognitive function was assessed using the object recognition test.
• Neuroinflammation markers, blood-brain barrier integrity, and hippocampal GABA levels were analyzed via transcriptomics, Western blot, and liquid chromatography-mass spectrometry.

Main Results:

• Obesity increased neuroinflammatory markers in the hippocampus and hypothalamus, alongside cognitive deficits.
• Western blot suggested the obesogenic diet disrupted the blood-brain barrier and increased Toll-like receptor 4 in the hippocampus.
• CR intervention reversed neuroinflammatory changes and cognitive impairments, increasing hippocampal GABA levels.

Conclusions:

• Caloric restriction shows promise as a therapeutic intervention for neuroinflammation and cognitive deficits associated with obesity in aging.
• CR may ameliorate brain alterations by modulating neuroinflammatory pathways and increasing GABAergic signaling in the hippocampus.