In Vivo Measurement of Neurochemical Abnormalities in the Hippocampus in a Rat Model of Cuprizone-Induced Demyelination

This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo 7 T proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow di...

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Main Authors: Do-Wan Lee, Jae-Im Kwon, Chul-Woong Woo, Hwon Heo, Kyung Won Kim, Dong-Cheol Woo, Jeong Kon Kim, Dong-Hoon Lee
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Diagnostics
Subjects:
Online Access:https://www.mdpi.com/2075-4418/11/1/45
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author Do-Wan Lee
Jae-Im Kwon
Chul-Woong Woo
Hwon Heo
Kyung Won Kim
Dong-Cheol Woo
Jeong Kon Kim
Dong-Hoon Lee
author_facet Do-Wan Lee
Jae-Im Kwon
Chul-Woong Woo
Hwon Heo
Kyung Won Kim
Dong-Cheol Woo
Jeong Kon Kim
Dong-Hoon Lee
author_sort Do-Wan Lee
collection DOAJ
description This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo 7 T proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow diet or cuprizone (0.2%, w/w) for 7 weeks. Demyelinated hippocampal lesions were quantitatively measured using a 7 T magnetic resonance imaging scanner. All proton spectra were quantified for metabolite concentrations and relative ratios. Compared to those in the controls, the cuprizone-induced rats had significantly higher concentrations of glutamate (<i>p</i> = 0.001), gamma-aminobutyric acid (<i>p</i> = 0.019), and glutamate + glutamine (<i>p</i> = 0.001); however, creatine + phosphocreatine (<i>p</i> = 0.006) and myo-inositol (<i>p</i> = 0.001) concentrations were lower. In addition, we found that the glutamine and glutamate complex/total creatine (<i>p</i> < 0.001), glutamate/total creatine (<i>p</i> < 0.001), and GABA/total creatine (<i>p</i> = 0.002) ratios were significantly higher in cuprizone-treated rats than in control rats. Our results showed that cuprizone-induced neuronal demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation, mitochondrial dysfunction, and astrocytic necrosis.
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spelling doaj.art-c425ab8a10f5402bbae2752dcfb3e39e2023-11-21T03:03:13ZengMDPI AGDiagnostics2075-44182020-12-011114510.3390/diagnostics11010045In Vivo Measurement of Neurochemical Abnormalities in the Hippocampus in a Rat Model of Cuprizone-Induced DemyelinationDo-Wan Lee0Jae-Im Kwon1Chul-Woong Woo2Hwon Heo3Kyung Won Kim4Dong-Cheol Woo5Jeong Kon Kim6Dong-Hoon Lee7Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaConvergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, KoreaConvergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, KoreaDepartment of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaConvergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, KoreaDepartment of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Radiation Convergence Engineering, Yonsei University, Wonju 26493, KoreaThis study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo 7 T proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow diet or cuprizone (0.2%, w/w) for 7 weeks. Demyelinated hippocampal lesions were quantitatively measured using a 7 T magnetic resonance imaging scanner. All proton spectra were quantified for metabolite concentrations and relative ratios. Compared to those in the controls, the cuprizone-induced rats had significantly higher concentrations of glutamate (<i>p</i> = 0.001), gamma-aminobutyric acid (<i>p</i> = 0.019), and glutamate + glutamine (<i>p</i> = 0.001); however, creatine + phosphocreatine (<i>p</i> = 0.006) and myo-inositol (<i>p</i> = 0.001) concentrations were lower. In addition, we found that the glutamine and glutamate complex/total creatine (<i>p</i> < 0.001), glutamate/total creatine (<i>p</i> < 0.001), and GABA/total creatine (<i>p</i> = 0.002) ratios were significantly higher in cuprizone-treated rats than in control rats. Our results showed that cuprizone-induced neuronal demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation, mitochondrial dysfunction, and astrocytic necrosis.https://www.mdpi.com/2075-4418/11/1/45rat braindemyelinationhippocampusmetabolitesmultiple sclerosis
spellingShingle Do-Wan Lee
Jae-Im Kwon
Chul-Woong Woo
Hwon Heo
Kyung Won Kim
Dong-Cheol Woo
Jeong Kon Kim
Dong-Hoon Lee
In Vivo Measurement of Neurochemical Abnormalities in the Hippocampus in a Rat Model of Cuprizone-Induced Demyelination
Diagnostics
rat brain
demyelination
hippocampus
metabolites
multiple sclerosis
title In Vivo Measurement of Neurochemical Abnormalities in the Hippocampus in a Rat Model of Cuprizone-Induced Demyelination
title_full In Vivo Measurement of Neurochemical Abnormalities in the Hippocampus in a Rat Model of Cuprizone-Induced Demyelination
title_fullStr In Vivo Measurement of Neurochemical Abnormalities in the Hippocampus in a Rat Model of Cuprizone-Induced Demyelination
title_full_unstemmed In Vivo Measurement of Neurochemical Abnormalities in the Hippocampus in a Rat Model of Cuprizone-Induced Demyelination
title_short In Vivo Measurement of Neurochemical Abnormalities in the Hippocampus in a Rat Model of Cuprizone-Induced Demyelination
title_sort in vivo measurement of neurochemical abnormalities in the hippocampus in a rat model of cuprizone induced demyelination
topic rat brain
demyelination
hippocampus
metabolites
multiple sclerosis
url https://www.mdpi.com/2075-4418/11/1/45
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