Author/Authors :
Nikasa، Mitra نويسنده Higher Academic Education Institute of Rabe Rashid,
Tabriz, IR Iran , , Karimi، Pouran نويسنده Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran. , , Rajavand، Hosnieh نويسنده Higher Academic Education Institute of Rabe Rashid,
Tabriz, IR Iran , , Afshari، Fatemeh نويسنده Department of Histopathology, Tabriz Medical Sciences
Branch, Islamic Azad University, Tabriz, IR Iran , , Jafarlou، Mahdi نويسنده Faculty of Medicine and Health Sciences, UPM, Serdang,
Malaysia , , Soltanali، Mahboob نويسنده Higher Academic Education Institute of Rabe Rashid,
Tabriz, IR Iran ,
Abstract :
Abnormal cholesterol homeostasis is associated with the
pathogenesis of neurodegenerative disease and cognitive impairment. Our
objective was to evaluate changes in the expression of proteins related
to cognition and cholesterol homeostasis in the hippocampi of rats as
well as behavioral modifications following the administration of a
cholesterol-rich diet. 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 of the
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 well as brain TC were measured by colorimetric assay. After a
high cholesterol diet had been administered for a period of 16 weeks, a
significant increase in TC, LDL-C and TG was observed in the HD group in
comparison with the ND group (P < 0.05). Neither the mean of
brain wet weight nor brain TC showed significant change in the HD versus
the ND group (P = 0.114, P = 0.84, respectively). Despite this fixity,
differences in the expression of BACE1 and CYP46A1 were significant (P
< 0.05) between the two groups, with high levels of BACE1 and
CYP46A1 in the HD group compared with the ND group. These biochemical
changes were associated with a significant decrease in the time traveled
on a platform quadrant in the HD versus the ND group (P < 0.05)
during a spatial memory probe test administered at the same time. The
findings show that irregularities in cognitive performance as a result
of a high cholesterol diet can be partially mediated by distortion in
brain cholesterol homeostasis and processing of the amyloid precursor
protein (APP).
