The Effects of a High-Energy Diet on Hippocampal Function and Blood-Brain Barrier Integrity in the Rat

J Alzheimers Dis. 2010;21(1):207-19. doi: 10.3233/JAD-2010-091414.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Animal
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / physiopathology*
  • Body Weight
  • Cognition Disorders / etiology*
  • Cognition Disorders / pathology*
  • Dietary Fats / adverse effects*
  • Discrimination Learning / physiology
  • Disease Models, Animal
  • Food Deprivation
  • Gene Expression Regulation / physiology
  • Hippocampus / metabolism*
  • Male
  • Maze Learning / physiology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tight Junctions / metabolism
  • Time Factors


  • Dietary Fats
  • Membrane Proteins