Abstract
BackgroundHypercholesterolemia is known to increase the risk of AD in later life, the purpose of this study is to illustrate brain metabolic and structural changes in a cholesterol-fed rabbit model of Alzheimer’s Disease (AD) by using clinical 3 T Magnetic Resonance Imaging (MRI).MethodsThe Institutional Animal Care and Use Committee of Zhejiang Chinese Medical University approved the study. Totally 16 Japanese White Rabbits (JWR) were randomly divided into 2 groups including normal control group fed with routine diet (group NC) and high cholesterol diet group (group CD) fed a 2% cholesterol diet with 0.24 ppm copper in the drinking water for 12 weeks. Magnetic resonance spectroscopy (MRS) and structural image of rabbit brain were performed by using a 3 Tesla (T) MRI scanner with an 8 channel Rabbit coil. The chemical metabolites were identified by LC Model including N-acetylaspartate (NAA), creatine (Cr), glutamate (Glu), glutamine (Gln), Glycerophosphatidylcholine (GPC), phosphorylcholine (PCH), and myoinositol (MI). The relative concentrations (/Cr) were analyzed. Additionally, Amyloid-β (Aβ) accumulation in the brain was measured postmortem. For comparisons of MR and Aβ data between groups, two-tailed t-tests were performed.ResultsThe ratio of NAA/Cr (0.76 ± 0.10) and Glu/Cr (0.90 ± 0.14) in group CD were lower than those in the group NC (0.87 ± 0.06, 1.13 ± 0.22, respectively, P < 0.05). Compared to the group NC (2.88 ± 0.09 cm3, 0.63 ± 0.08 cm3, respectively), the cortical and hippocampal volumes (2.60 ± 0.14 cm3 and 0.47 ± 0.07 cm3, respectively) of rabbits brain decreased in the group CD while the third and lateral ventricular volumes enlarged (44.56 ± 6.01 mm3 vs 31.40 ± 6.14 mm3, 261.40 ± 30.98 mm3 vs 153.81 ± 30.08 mm3, P < 0.05). These metabolic and structural changes were additionally accompanied by the significant increase of Aβ1–42 in the cortex and hippocampus (163.60 ± 16.26 pg/mg and 215.20 ± 69.86 pg/mg, respectively, P < 0.05).ConclusionHigh cholesterol diet can induce the brain metabolic and structural changes of the rabbit including lowered level of NAA and Glu and the atrophy of the brain which were similar to those of human AD.
Highlights
Hypercholesterolemia is known to increase the risk of AD in later life, the purpose of this study is to illustrate brain metabolic and structural changes in a cholesterol-fed rabbit model of Alzheimer’s Disease (AD) by using clinical 3 T Magnetic Resonance Imaging (MRI)
A growing body of evidence supports the claim that cholesterol metabolism plays a leading role in AD pathogenesis [7,8,9]
8 Japanese White Rabbits (JWR) were fed 120 g/day of rabbit chow supplemented with 2% cholesterol
Summary
Hypercholesterolemia is known to increase the risk of AD in later life, the purpose of this study is to illustrate brain metabolic and structural changes in a cholesterol-fed rabbit model of Alzheimer’s Disease (AD) by using clinical 3 T Magnetic Resonance Imaging (MRI). As the processing of profound studies on the role of diet and nutraceuticals, the association of the high cholesterol diet or hypercholesterolemia with neurocognitive dysfunction, cardiovascular and other metabolic diseases has been reported [5, 6]. A growing body of evidence supports the claim that cholesterol metabolism plays a leading role in AD pathogenesis [7,8,9]. Many cholesterol-fed animal models of AD have been established to study the pathophysiology of AD [13,14,15]
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