Effect of high cholesterol diet on spatial learning and memory in a rat model of Alzheimer's disease

BACKGROUND: Recently Study indicates a potentially important link between cholesterol, A beta deposit, and clinicopathological manifestation of Alzheimer's disease (AD). OBJECTIVE: To Study the effect of high cholesterol diet on cognitive function and neuronal loss of hippocampal dentate gyrus in AD model rats. DESIGN, TIME AND SETTING: A randomized controlled animal study, which was performed in the Laboratory of Stem Cells, Department of Pathology, Third Military Medical University of Chinese PLA from February 2006 to March 2007. MATERIALS: Twenty healthy, male, Wistar rats, aged 3-4 months and weighing (300 +/- 20) g, were selected for this study. A beta(1-40) was provided by Sigma Company, USA. Standard diet and high cholesterol diet mixed with cholesterol (5%), sodium hypocholic acid (1%), lard (10%), and ordinary rat food (84%) were provided by Experimental Animal Center, Institute of Field Surgery, Daping Hospital, Third Military Medical University of Chinese PLA. METHODS: Rats were fed on high cholesterol diet or standard diet for eight successive weeks. Then, rats were randomly divided into cholesterol diet +A beta, high cholesterol diet + phosphate buffered saline(PBS), standard diet + A beta, and standard diet + PBS group, with five rats in each group. AD rat models were established by local injection of A beta(1-40) solution (10 mu L) into the hippocampal dentate gyrus. Rats in the control group were injected with the same volume of PBS. After injection, rat were fed for two weeks MAIN OUTCOME MEASURES: Neuronal cells in the hippocampal dentate gyrus were detected by Nissl staining; spatial navigation and spatial probe were detected by Morris water maze to reflect learning and memory. RESULTS: Twenty rats were included in the final analysis, without any loss. (1) Neuronal numbers: neuronal loss in the high cholesterol diet + A beta and standard diet + A beta groups was significantly higher than in the PBS groups (P < 0.01). In particular, loss of pyramidal cells in the high cholesterol diet + A beta group was significantly higher than in the standard diet + A beta group (P < 0.0 1). (2) Average escape latency: average escape latency was ranked as follows: cholesterol diet + A beta; group > standard diet + A beta group > high cholesterol diet + PBS group > standard diet + PBS group. Moreover, the number of occasions on which the platform was passed-as well as percentage of swimming distance between two quadrants within two minutes-negatively correlated with average escape latency. CONCLUSION: High cholesterol diet may accelerate neuronal loss in the hippocampal dentate gyrus and aggravate cognitive impairment in AD rats.