Effects of high fat diet on cognition and brain pathology

Abstract

Consumption of a high fat diet in western countries has increased significantly over the past few decades, leading to major health issues. Recent evidence shows an association between obesity and cognitive decline. The present studies aimed to (i) determine whether high fat or western diet can affect working or spatial memory in rats (ii) investigate the changes that occur in brain areas important for memory regulation following the consumption of a higher percentage of fat in diet. Male Long Evan and Hooded-Wistar rats were fed normal chow, western diet (23% fat, 0.19% cholesterol) or high fat diet (60% fat) for 12 weeks. Body weight and food intake were measured twice weekly. Behavioural testing was carried out after 12 weeks of feeding by investigating (i) working memory performance in the novel object recognition test, (ii) spatial memory using a Y-maze and (iii) rewarded alternation using a T-maze. In one cohort of rats the Y-maze and novel object recognition tasks were repeated at the end of each month of feeding for three months to find out at what point during the feeding, the memory impairment begins. Immunohistochemistry was carried out in specific brain areas including those that are important in memory regulation in order to investigate the changes in the level of cholinergic markers, basal neuronal activity, astrocytes and insulin like growth factor 1 receptor. This research was the first to report an impairment of spatial memory using a Y-maze paradigm in rats following the consumption of a western or high fat diet for three months. Further investigation revealed that consumption of these diets is associated with changes in specific areas of the brain including those that are involved in memory regulation. These changes include the increased level of acetylcholinesterase in the striatum, the reduced number of GFAP-positive astrocytes in CA1 and dentate gyrus of the hippocampus besides the decreased level of basal neuronal activity in CA2&3 region of the hippocampus, prelimbic and infralimbic areas of the prefrontal cortex and in the paraventricular nucleus of thalamus in rats following consumption of high fat or western diets. Overall, these results suggest that higher percentage of fat in diet can affect specific regions of the brain that are important for memory regulation through various mechanisms and consequently may affect the memory