The effects of a high-energy diet on hippocampal-dependent negative occasion setting and blood-brain barrier integrity in the rat

Intake of saturated fats and simple carbohydrates, two of the primary components of a modern Western diet, is associated with cognitive impairments in both humans and nonhuman animals. In rats, these dietary components have been shown to disrupt hippocampal-dependent learning and memory processes, particularly those involving spatial information. Little is known about their effects on cognitive processes that do not require an intact hippocampus. Furthermore, the effects of brief periods of consumption of this type of diet on learning and memory function are not yet established. The present research examined the impact on rats of both short- and longer-term maintenance on a high-energy (HE) diet, which is high in saturated fat and glucose, compared to a standard chow diet in learning and memory performance in three Pavlovian discrimination problems that differed with respect to their dependence on the integrity of the hippocampus. Memory retention was impaired in a hippocampal-dependent feature negative discrimination (A+, X→A-) following less than two-weeks consumption of an HE-diet, whereas performance was not affected in a feature positive (A-, X→A+) and a nonconditional (B+, C-) discrimination, both of which do not require an intact hippocampus. Maintenance on the HE-diet for over three months produced more profound impairments in acquisition learning of the feature negative discrimination, but did not influence acquisition of the other two discriminations. The present research also explored the hypothesis that the effects of consuming HE-diets on hippocampal function are linked to impaired blood-brain barrier (BBB) impairment. We found that over 90 days of HE-diet consumption produced a decrease in mRNA expression of tight junction proteins, particularly Claudin 5 and 12, in the blood-cerebrospinal fluid (CSF) and blood-brain barriers. Increased barrier permeability of sodium fluorescein was also observed in the hippocampus, but not in the striatum and the prefrontal cortex following longer but not shorter-term access to the HE-diet. These results show that hippocampal function is particularly vulnerable to disruption by HE-diets, and this disruption may be related to impaired BBB integrity. Furthermore, consumption of an HE-diet may interfere with the higher-order, learned controls of energy regulation by disrupting hippocampal-dependent negative occasion setting