Effects of a Saturated Fat and High Cholesterol Diet on Memory and Hippocampal Morphology in the Middle-Aged Rat

Abstract

Diets rich in cholesterol and/or saturated fats have been shown to be detrimental to cognitive performance. Therefore, we fed a cholesterol (2%) and saturated fat (hydrogenated coconut oil, Sat Fat 10%) diet to 16-month old rats for 8 weeks to explore the effects on the working memory performance of middle-aged rats. Lipid profiles revealed elevated plasma triglycerides, total cholesterol, HDL, and LDL for the Sat-Fat group as compared to an iso-caloric control diet (12% soybean oil). Weight gain and food consumption were similar in both groups. Sat-Fat treated rats committed more working memory errors in the water radial arm maze, especially at higher memory loads. Cholesterol, amyloid-β peptide of 40 (Aβ40) or 42 (Aβ42) residues, and nerve growth factor in cortical regions was unaffected, but hippocampal Map-2 staining was reduced in rats fed a SatFat diet, indicating a loss of dendritic integrity. Map-2 reduction correlated with memory errors. Microglial activation, indicating inflammation and/or gliosis, was also observed in the hippocampus of Sat-Fat fed rats. These data suggest that saturated fat, hydrogenated fat and cholesterol can profoundly impair memory and hippocampal morphology.

Short-Term High-Fat-and-Fructose Feeding Produces Insulin Signaling Alterations Accompanied by Neurite and Synaptic Reduction and Astroglial Activation in the Rat Hippocampus

“…33,34 In particular, it was reported that rats fed with a high-fat diet (soybean oil and cholesterol supplemented, no fructose) for 8 weeks present a diminished staining of MAP-2 in the hippocampus, and that this reduction is correlated with memory errors. 16 Microtubule-associated protein 2 modifies and controls microtubule assembly and spacing within dendrites. Thus, a fine regulation of MAP-2 dynamics can alter hippocampal plasticity.…”

“…[7][8][9][10] Studies performed in animal models of diet-induced obesity and InsRes such as longterm HFFD feeding show a deficient execution in memory and learning tasks. [11][12][13][14][15][16] These cognitive alterations were associated with functional and structural changes in the hippocampus, such as reduced number and complexity of dendritic spines in the CA1 subfield, altered establishment of long-term potentiation and long-term depression, and diminished dentate gyrus (DG) neurogenesis. [11][12][13] The latter was correlated with decreased expression of brain derived neurotrophic factor, cyclic AMP-response element-binding protein and the synaptic proteins synapsin, and stargazin.…”

High-Fat and Cholesterol Intake Affects Brain Homeostasis and Could Accelerate the Development of Dementia: A Systemic View

“…The researchers evaluate the effect of a diet high in cholesterol and fat (diet containing 2% cholesterol and 10% hydrogenated coconut oil). The results showed a failure in working memory, here evaluated with the water radial arm maze as well as elevated lipids profile and reduce expression of Map-2 as an indicator of alteration of dendritic integrity, which correlates with memory mistakes measured in the test, and increase in inflammation markers such as microglia activation [52]. In a study carried out with Sprague-Dawley rats, which were fed for 7 days with high fat and fructose, several hippocampal alterations, such as decreased insulin signaling, were reported.…”

Impaired Adaptive Cellular Responses to Oxidative Stress and the Pathogenesis of Alzheimer's Disease

“…Murray et al showed that only 9 days of a high-fat diet was sufficient to cause physical impairment on a treadmill and cognitive impairment in the water maze (121). When 16-month-old rats were fed diets high in fat and cholesterol they made more errors in a test of working memory especially when memory loads were high, and they also showed altered hippocampal morphology (60). Similar studies of mice showed that high-fat diets worsen performance in learning and memory tests (49,181).…”