Affiliations: [a] Department of Psychological Sciences, Purdue University, West Lafayette, IN, USA | [b] School of Health Sciences, Purdue University, West Lafayette, IN, USA
Correspondence:
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Correspondence to: Scott E. Kanoski, University of Pennsylvania, The Department of Psychology, 3720 Walnut Street, Solomon Lab Building, Philadelphia, PA 19104-6241, USA. Tel.: +1 215 898 8617; Fax: +1 215 898 5957; E-mail: [email protected].
Abstract: Cognitive impairment and Alzheimer's disease are linked with intake of a Western diet, characterized by high levels of saturated fats and simple carbohydrates. In rats, these dietary components have been shown to disrupt hippocampal-dependent learning and memory processes, particularly those involving spatial memory. Using a rat model, the present research assessed the degree to which consumption of a high-energy (HE) diet, similar to those found in modern Western cultures, produces a selective impairment in hippocampal function as opposed to a more global cognitive disruption. Learning and memory performance was examined following 90-day consumption of an HE-diet in three nonspatial discrimination learning problems that differed with respect to their dependence on the integrity of the hippocampus. The results showed that consumption of the HE-diet impaired performance in a hippocampal-dependent feature negative discrimination problem relative to chow-fed controls, whereas performance was spared on two discrimination problems that do not rely on the hippocampus. To explore the mechanism whereby consuming HE-diets impairs cognitive function, we investigated the effect of HE-diets on the integrity of the blood-brain barrier (BBB). We found that HE-diet consumption produced a decrease in mRNA expression of tight junction proteins, particularly Claudin-5 and -12, in the choroid plexus and the BBB. Consequently, an increased blood-to-brain permeability of sodium fluorescein was observed in the hippocampus, but not in the striatum and prefrontal cortex following HE-diet access. These results indicate that hippocampal function may be particularly vulnerable to disruption by HE-diets, and this disruption may be related to impaired BBB integrity.
Keywords: Alzheimer's disease, amyloid-β, blood-brain barrier, choroid plexus, dementia, high fat diet, hippocampus, learning, occasion setting, Western diet
