High Cholesterol Diet Increases Expression of Cholesterol 24-Hydroxylase and BACE1 in Rat Hippocampi: Implications for the Effect of Diet Cholesterol on Memory
نویسندگان
1 Higher Academic Education Institute of Rabe Rashid, Tabriz, IR Iran
2 Faculty of Medicine and Health Sciences, UPM, Serdang, Malaysia
3 Higher Academic Education Institute of Rabe Rashid, Tabriz, IR Iran
4 Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, IR Iran
5 Higher Academic Education Institute of Rabe Rashid, Tabriz, IR Iran
6 Department of Histopathology, Tabriz Medical Sciences Branch, Islamic Azad University, Tabriz, IR Iran
doi
چکیده
Background: Abnormal cholesterol homeostasis is associated with the pathogenesis of neurodegenerative disease and cognitiveimpairment.Objectives: Our objective was to evaluate changes in the expression of proteins related to cognition and cholesterol homeostasisin the hippocampi of rats as well as behavioral modifications following the administration of a cholesterol-rich diet.Methods: In this experimental study, lasting 16 weeks, 20 male Wistar rats (aged 8 weeks) were randomly divided into two groups.One group was fed with a normal diet (ND; n = 10) and the second with a high cholesterol diet (HD; n = 10). The expression ofthe cognition-related proteins N-methyl-D-aspartate receptor (NMDAR) and beta-secretase 1 (BACE1) and cholesterol 24-hydroxylase(CYP46A1), the key cholesterol hemostasis protein, were determined by an immunoblotting assay in the hippocampus homogenate.The Morris water maze (MWM) test was used to examine cognitive performance. Plasma lipidic parameters, including total cholesterol(TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG), as wellas brain TC were measured by colorimetric assay.Results: After a high cholesterol diet had been administered for a period of 16 weeks, a significant increase in TC, LDL-C and TG wasobserved in the HD group in comparison with the ND group (P < 0.05). Neither the mean of brain wet weight nor brain TC showedsignificant change in the HD versus the ND group (P = 0.114, P = 0.84, respectively). Despite this fixity, differences in the expressionof BACE1 and CYP46A1 were significant (P < 0.05) between the two groups, with high levels of BACE1 and CYP46A1 in the HD groupcompared with the ND group. These biochemical changes were associated with a significant decrease in the time traveled on aplatform quadrant in the HD versus the ND group (P < 0.05) during a spatial memory probe test administered at the same time.Conclusions: The findings show that irregularities in cognitive performance as a result of a high cholesterol diet can be partiallymediated by distortion in brain cholesterol homeostasis and processing of the amyloid precursor protein (APP).
