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Alzheimer-like brain metabolic and structural features in cholesterol-fed rabbit detected by magnetic resonance imaging

BACKGROUND: 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). METHODS: The Ins...

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Autores principales: Jin, Ping, Pan, Yongming, Pan, Zhiyong, Xu, Jianqin, Lin, Min, Sun, Zhichao, Chen, Minli, Xu, Maosheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870103/
https://www.ncbi.nlm.nih.gov/pubmed/29587752
http://dx.doi.org/10.1186/s12944-018-0705-9
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author Jin, Ping
Pan, Yongming
Pan, Zhiyong
Xu, Jianqin
Lin, Min
Sun, Zhichao
Chen, Minli
Xu, Maosheng
author_facet Jin, Ping
Pan, Yongming
Pan, Zhiyong
Xu, Jianqin
Lin, Min
Sun, Zhichao
Chen, Minli
Xu, Maosheng
author_sort Jin, Ping
collection PubMed
description BACKGROUND: 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). METHODS: The 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. RESULTS: The 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 cm(3), 0.63 ± 0.08 cm(3), respectively), the cortical and hippocampal volumes (2.60 ± 0.14 cm(3) and 0.47 ± 0.07 cm(3), respectively) of rabbits brain decreased in the group CD while the third and lateral ventricular volumes enlarged (44.56 ± 6.01 mm(3) vs 31.40 ± 6.14 mm(3), 261.40 ± 30.98 mm(3) vs 153.81 ± 30.08 mm(3), 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). CONCLUSION: High 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.
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spelling pubmed-58701032018-03-29 Alzheimer-like brain metabolic and structural features in cholesterol-fed rabbit detected by magnetic resonance imaging Jin, Ping Pan, Yongming Pan, Zhiyong Xu, Jianqin Lin, Min Sun, Zhichao Chen, Minli Xu, Maosheng Lipids Health Dis Research BACKGROUND: 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). METHODS: The 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. RESULTS: The 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 cm(3), 0.63 ± 0.08 cm(3), respectively), the cortical and hippocampal volumes (2.60 ± 0.14 cm(3) and 0.47 ± 0.07 cm(3), respectively) of rabbits brain decreased in the group CD while the third and lateral ventricular volumes enlarged (44.56 ± 6.01 mm(3) vs 31.40 ± 6.14 mm(3), 261.40 ± 30.98 mm(3) vs 153.81 ± 30.08 mm(3), 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). CONCLUSION: High 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. BioMed Central 2018-03-27 /pmc/articles/PMC5870103/ /pubmed/29587752 http://dx.doi.org/10.1186/s12944-018-0705-9 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Jin, Ping
Pan, Yongming
Pan, Zhiyong
Xu, Jianqin
Lin, Min
Sun, Zhichao
Chen, Minli
Xu, Maosheng
Alzheimer-like brain metabolic and structural features in cholesterol-fed rabbit detected by magnetic resonance imaging
title Alzheimer-like brain metabolic and structural features in cholesterol-fed rabbit detected by magnetic resonance imaging
title_full Alzheimer-like brain metabolic and structural features in cholesterol-fed rabbit detected by magnetic resonance imaging
title_fullStr Alzheimer-like brain metabolic and structural features in cholesterol-fed rabbit detected by magnetic resonance imaging
title_full_unstemmed Alzheimer-like brain metabolic and structural features in cholesterol-fed rabbit detected by magnetic resonance imaging
title_short Alzheimer-like brain metabolic and structural features in cholesterol-fed rabbit detected by magnetic resonance imaging
title_sort alzheimer-like brain metabolic and structural features in cholesterol-fed rabbit detected by magnetic resonance imaging
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870103/
https://www.ncbi.nlm.nih.gov/pubmed/29587752
http://dx.doi.org/10.1186/s12944-018-0705-9
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