In a recent study published in the journal Brain, Behavior, and Immunity, researchers developed an initial-life Western diet (WD) murine model associated with long-term hippocampal (HPC) dysfunction to examine the neurobiological processes underlying these effects.
Study: Western diet consumption impairs memory function via dysregulated hippocampus acetylcholine signaling
The Western diet, abundant in processed foods, saturated fat, and simple carbohydrates, has been linked to poor memory performance, particularly in hippocampus-dependent functions. The neurobiological processes underlying Western diet during development, which contribute to long-term hippocampus damage, remain unknown. WD-associated changes in HPC neuronal functions have been discovered, including synaptic plasticity alterations, decreased brain-derived neurotrophic factor (BDNF) levels, and increased neuro-inflammation markers. Disruptions in acetylcholine (ACh) signaling may contribute to long-term Western diet-associated memory impairment.
About the study
In the present study, researchers investigated the long-term effects of early-life Western diet intake on hippocampal episodic memory and the mediating effects of hippocampal acetylcholine signaling dysregulation on behavioral consequences.
The study used a relevant Western diet model incorporating dietary choice (from several sugar-dense and fatty foods and drink alternatives) and macronutrients that simulate a current human WD to investigate whether the gut microbiota functionally associates with early childhood WD-induced memory deficits, possibly through alterations in HPC ACh activity.
To depict an initial-life Western diet model in rats, the researchers adopted the 'junk food' cafeteria-style diet (CAF). During the juvenile and teenage periods (postnatal days 26–56), rats were fed a cafeteria-style diet (with ad libitum intake of high-fat and high-sugar items; CAF) or regular chow (CTL). The researchers conducted metabolic and behavioral evaluations before and following a healthy eating intervention that began in early adulthood. They provided control rats (CTL) with the same amount of food and beverage receptacles but filled them with regular chow.
The team monitored body weight and food intake three times a week. They estimated the total kilocalorie content ingested from each CAF diet component by multiplying food and drink weights for every rodent by the component's energy density. They computed kilocalorie consumption from every macronutrient for CAF-fed animals based on kilocalorie intake per CAF diet component and the macronutrient composition of each. Memory problems were sustained even after 30 days of healthy eating in the first group, and subsequent cohorts were administered Western diets until 30 days (PN 56). The researchers assessed protein indicators of acetylcholine tone in CAF and CTL rats' dorsal HPCs (HPCd). They used novel object in context (NOIC) to evaluate HPC-dependent contextual episodic memory and novel location recognition (NLR) to assess spatial recognition memory.
Researchers explored the role of ACh neurotransmission in the human brain (HBC) and its possible impact on memory performance. They investigated the amounts of proteins involved in ACh signaling in the HPC and conducted correlational studies between important microbial taxa and VAChT levels. They also explored changes in acute ACh signaling dynamics throughout an episodic memory challenge in CAF versus CTL rats. After a 30-day healthy dietary intervention, they measured ACh signaling using fiber photometry in vivo. The researchers also investigated whether pharmacological treatment of ACh receptor agonists may reverse long-term memory problems in CAF rodents.
Results
The study found that initial-life hydrocortical WD (hydrocortical WD) intake causes long-term abnormalities in hippocampus-dependent memory performance in CAF rodents, independent of a healthy dietary intervention. The researchers observed significant differences in spatial recognition memory using NLR and NOIC, indicating that initial-life Western diet intake does not result in robust discrepancies in recognizing a novel item in memory tests that did not engage the HPC.
Early childhood WD did not affect locomotor activity indicators or anxiety, implying that chronic HPC-dependent memory deficits caused by WD are unaffected by changed anxiety-like mannerisms or locomotor activity. The researchers also detected gut microbiome changes in CAF animals, with significant variations at the genus level between CAF animals and controls. However, these early significant differences showed reversal following the healthy dietary intervention. Correlational studies between particular taxons and memory performances in the NOIC test after the initial life Western diet access duration remained significant after FDR adjustment. Bifidobacterium and Lactococcus abundances showed negative associations with NOIC-evaluated memory ability, but Lactobacillus intestinalis showed positive associations.
Early childhood WD causes long-term decreases in the chronic HPC ACh signaling tone. Immunoblotting examinations of dorsal HPC tissue obtained during the healthy dietary intervention period indicated no variations in ChAT or AChE levels; however, CAF rats exhibited lower levels of VAChT than CTL rats. Early childhood WD alters acute ACh signaling patterns during memory testing, resulting in lower performance among CAF rats.
The study found that early exposure to a Western diet (WD) was associated with long-term episodic memory deficits mediated by altered hippocampal acetylcholine (ACh) transmission. The α7 nicotinic receptor is a critical mediator of WD-induced memory dysfunction. The gut flora is unlikely to be involved in the long-term HPC dysfunction associated with early childhood WD. Further research is required to improve understanding of the functional relationship between abnormal HPC ACh signaling and WD-associated memory deficits among females.
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