Western diet consumption impairs memory function via dysregulated hippocampus acetylcholine signaling

Area of Science:

• Neuroscience
• Developmental Biology
• Nutritional Science

Background:

• Long-term memory impairments result from early life Western diet (WD) consumption, but the neurobiological causes are unclear.
• Hippocampus (HPC) acetylcholine (ACh) signaling is crucial for memory and is impaired in dementia.
• This study investigates if disrupted HPC ACh signaling mediates WD-induced cognitive deficits in a rodent model.

Approach:

• Juvenile and adolescent rats were fed a Western diet (CAF) or healthy chow (CTL).
• Behavioral, metabolic, and microbiome changes were assessed before and after a healthy diet intervention.
• Hippocampus ACh signaling was measured using in vivo fiber photometry and receptor agonist treatment.

Key Points:

• Early WD consumption induced persistent hippocampus-dependent memory impairments, unaffected by later healthy diet, body weight, or metabolic changes.
• Reduced vesicular ACh transporter in the hippocampus indicated chronically impaired ACh signaling.
• Disrupted ACh signaling dynamics in the hippocampus during memory tasks predicted performance deficits.

Conclusions:

• Dysregulated hippocampus acetylcholine signaling is a key mechanism underlying memory impairments from early life Western diet exposure.
• Pharmacological activation of alpha-7 nicotinic receptors in the hippocampus rescued memory deficits.
• These findings reveal a critical link between early nutrition and long-term cognitive health via cholinergic pathways.