Abstract
Excessive consumption of diets high in saturated fat and sugar impairs short-term spatial recognition memory in both humans and rodents. Several studies have identified associations between the observed behavioral phenotype and diet-induced changes in adiposity, hippocampal gene expression of inflammatory and blood–brain barrier-related markers, and gut microbiome composition. However, the causal role of such variables in producing cognitive impairments remains unclear. As intermittent cafeteria diet access produces an intermediate phenotype, we contrasted continuous and intermittent diet access to identify specific changes in hippocampal gene expression and microbial species that underlie the cognitive impairment observed in rats fed continuous cafeteria diet. Female adult rats were fed either regular chow, continuous cafeteria diet, or intermittent cafeteria diet cycles (4 days regular chow and 3 days cafeteria) for 7 weeks (12 rats per group). Any cafeteria diet exposure affected metabolic health, hippocampal gene expression, and gut microbiota, but only continuous access impaired short-term spatial recognition memory. Multiple regression identified an operational taxonomic unit, from species Muribaculum intestinale, as a significant predictor of performance in the novel place recognition task. Thus, contrasting intermittent and continuous cafeteria diet exposure allowed us to identify specific changes in microbial species abundance and growth as potential underlying mechanisms relevant to diet-induced cognitive impairment.
Highlights
There is strong evidence that diets high in saturated fat and refined carbohydrates are associated with cognitive impairments in humans[1] and rodents[2,3], but the mechanisms underlying this association remain unclear
Results expressed as mean ± SEM; n = 11–12; data were analyzed by one-way analysis of variance (ANOVA) followed by Tukey-adjusted post-hoc testing
Hippocampal gene expression was assessed to determine whether diet affected markers of pro-inflammatory signaling, blood–brain barrier integrity, and synaptic function (Fig. 1c-e and Supplementary Table 1 for gene names). These results indicate that any exposure to cafeteria diet increases hippocampal cytokine expression, increased markers of astroglial and microglial proliferation, downstream pro-inflammatory signaling, and changes to blood–brain barrier integrity were unique to continuous cafeteria diet exposure
Summary
There is strong evidence that diets high in saturated fat and refined carbohydrates are associated with cognitive impairments in humans[1] and rodents[2,3], but the mechanisms underlying this association remain unclear. We and others have used rodent models to show that a western-style cafeteria diet, high in fat and sugar, promotes prolonged hyperphagia and increases adiposity, compromising metabolic health[4,5,6] Exposure to such diets impairs performance on hippocampal-dependent tasks assessing short-term spatial recognition[2,7] and reference[8,9] memory, as well as disrupting multiple hippocampal molecular pathways, including pro-inflammatory signaling[7,8,10], blood–brain barrier integrity[3,11] and synaptic transmission[12], and inducing fecal microbiome perturbations[13,14].
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