Abnormal oxidative metabolism in the cuprizone mouse model of demyelination: An in vivo NIRS-MRI study
Disruptions in oxidative metabolism may occur in multiple sclerosis and other demyelinating neurological diseases. The impact of demyelination on metabolic rate is also not understood. It is possible that mitochondrial damage may be associated with many such neurological disorders. To study oxidativ...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-04-01
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| Series: | NeuroImage |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1053811922000647 |
| _version_ | 1818987230123786240 |
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| author | Mada Hashem Qandeel Shafqat Ying Wu Jong M. Rho Jeff F. Dunn |
| author_facet | Mada Hashem Qandeel Shafqat Ying Wu Jong M. Rho Jeff F. Dunn |
| author_sort | Mada Hashem |
| collection | DOAJ |
| description | Disruptions in oxidative metabolism may occur in multiple sclerosis and other demyelinating neurological diseases. The impact of demyelination on metabolic rate is also not understood. It is possible that mitochondrial damage may be associated with many such neurological disorders. To study oxidative metabolism with one model of demyelination, we implemented a novel multimodal imaging technique combining Near-Infrared Spectroscopy (NIRS) and MRI to cuprizone mouse model. The cuprizone model is used to study demyelination and may be associated with inhibition of mitochondrial function. Cuprizone mice showed reduced oxygen extraction fraction (−39.1%, p ≤ 0.001), increased tissue oxygenation (6.4%, p ≤ 0.001), and reduced cerebral metabolic rate of oxygen in cortical gray matter (−62.1%, p ≤ 0.001). These changes resolved after the cessation of cuprizone exposure and partial remyelination. A decrease in hemoglobin concentration (−34.4%, p ≤ 0.001), but no change in cerebral blood flow were also observed during demyelination. The oxidized state of the mitochondrial enzyme, Cytochrome C Oxidase (CCO) increased (46.3%, p ≤ 0.001) while the reduced state decreased (−34.4%, p ≤ 0.05) significantly in cuprizone mice. The total amount of CCO did not change significantly during cuprizone exposure. Total CCO did decline after recovery both in control (−23.1%, p ≤ 0.01) and cuprizone (−28.8%, p ≤ 0.001) groups which may relate to age. A reduction in the magnetization transfer ratio, indicating demyelination, was found in the cuprizone group in the cerebral cortex (−3.2%, p ≤ 0.01) and corpus callosum (−5.5%, p ≤ 0.001). In summary, we were able to detect evidence of altered CCO metabolism during cuprizone exposure, consistent with a mitochondrial defect. We observed increased oxygenation and reduced metabolic rate associated with reduced myelination in the gray and white matter. The novel multimodal imaging technique applied here shows promise for noninvasively assessing parameters associated with oxidative metabolism in both mouse models of neurological disease and for translation to study oxidative metabolism in the human brain. |
| first_indexed | 2024-12-20T19:03:23Z |
| format | Article |
| id | doaj.art-27d0e39bb8bf4660b9bedefbf77cc20c |
| institution | Directory Open Access Journal |
| issn | 1095-9572 |
| language | English |
| last_indexed | 2024-12-20T19:03:23Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage |
| spelling | doaj.art-27d0e39bb8bf4660b9bedefbf77cc20c2022-12-21T19:29:20ZengElsevierNeuroImage1095-95722022-04-01250118935Abnormal oxidative metabolism in the cuprizone mouse model of demyelination: An in vivo NIRS-MRI studyMada Hashem0Qandeel Shafqat1Ying Wu2Jong M. Rho3Jeff F. Dunn4Biomedical Engineering Graduate Program, University of Calgary, Calgary, Alberta T2N 4N1, Canada; Department of Radiology, Faculty of Medicine, University of Calgary, 3330 Hospital Drive, N.W., Calgary, Alberta T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Alberta T2N 4N1, Canada; Experimental Imaging Centre, Cumming School of Medicine, University of Calgary, Alberta T2N 4N1, CanadaDepartment of Radiology, Faculty of Medicine, University of Calgary, 3330 Hospital Drive, N.W., Calgary, Alberta T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Alberta T2N 4N1, Canada; Experimental Imaging Centre, Cumming School of Medicine, University of Calgary, Alberta T2N 4N1, CanadaDepartment of Radiology, Faculty of Medicine, University of Calgary, 3330 Hospital Drive, N.W., Calgary, Alberta T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Alberta T2N 4N1, Canada; Experimental Imaging Centre, Cumming School of Medicine, University of Calgary, Alberta T2N 4N1, CanadaCumming School of Medicine, Alberta Children's Hospital Research Institute, University of Calgary, Alberta, T2N 4N1, CanadaDepartment of Radiology, Faculty of Medicine, University of Calgary, 3330 Hospital Drive, N.W., Calgary, Alberta T2N 4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Alberta T2N 4N1, Canada; Experimental Imaging Centre, Cumming School of Medicine, University of Calgary, Alberta T2N 4N1, Canada; Corresponding author at: Department of Radiology, Faculty of Medicine, University of Calgary, 3330 Hospital Drive, N.W., Calgary, Alberta T2N 4N1, Canada.Disruptions in oxidative metabolism may occur in multiple sclerosis and other demyelinating neurological diseases. The impact of demyelination on metabolic rate is also not understood. It is possible that mitochondrial damage may be associated with many such neurological disorders. To study oxidative metabolism with one model of demyelination, we implemented a novel multimodal imaging technique combining Near-Infrared Spectroscopy (NIRS) and MRI to cuprizone mouse model. The cuprizone model is used to study demyelination and may be associated with inhibition of mitochondrial function. Cuprizone mice showed reduced oxygen extraction fraction (−39.1%, p ≤ 0.001), increased tissue oxygenation (6.4%, p ≤ 0.001), and reduced cerebral metabolic rate of oxygen in cortical gray matter (−62.1%, p ≤ 0.001). These changes resolved after the cessation of cuprizone exposure and partial remyelination. A decrease in hemoglobin concentration (−34.4%, p ≤ 0.001), but no change in cerebral blood flow were also observed during demyelination. The oxidized state of the mitochondrial enzyme, Cytochrome C Oxidase (CCO) increased (46.3%, p ≤ 0.001) while the reduced state decreased (−34.4%, p ≤ 0.05) significantly in cuprizone mice. The total amount of CCO did not change significantly during cuprizone exposure. Total CCO did decline after recovery both in control (−23.1%, p ≤ 0.01) and cuprizone (−28.8%, p ≤ 0.001) groups which may relate to age. A reduction in the magnetization transfer ratio, indicating demyelination, was found in the cuprizone group in the cerebral cortex (−3.2%, p ≤ 0.01) and corpus callosum (−5.5%, p ≤ 0.001). In summary, we were able to detect evidence of altered CCO metabolism during cuprizone exposure, consistent with a mitochondrial defect. We observed increased oxygenation and reduced metabolic rate associated with reduced myelination in the gray and white matter. The novel multimodal imaging technique applied here shows promise for noninvasively assessing parameters associated with oxidative metabolism in both mouse models of neurological disease and for translation to study oxidative metabolism in the human brain.http://www.sciencedirect.com/science/article/pii/S1053811922000647Cuprizone mouse modelDemyelinationCerebral metabolic rate of oxygenCytochrome C oxidaseNIRSMRI |
| spellingShingle | Mada Hashem Qandeel Shafqat Ying Wu Jong M. Rho Jeff F. Dunn Abnormal oxidative metabolism in the cuprizone mouse model of demyelination: An in vivo NIRS-MRI study NeuroImage Cuprizone mouse model Demyelination Cerebral metabolic rate of oxygen Cytochrome C oxidase NIRS MRI |
| title | Abnormal oxidative metabolism in the cuprizone mouse model of demyelination: An in vivo NIRS-MRI study |
| title_full | Abnormal oxidative metabolism in the cuprizone mouse model of demyelination: An in vivo NIRS-MRI study |
| title_fullStr | Abnormal oxidative metabolism in the cuprizone mouse model of demyelination: An in vivo NIRS-MRI study |
| title_full_unstemmed | Abnormal oxidative metabolism in the cuprizone mouse model of demyelination: An in vivo NIRS-MRI study |
| title_short | Abnormal oxidative metabolism in the cuprizone mouse model of demyelination: An in vivo NIRS-MRI study |
| title_sort | abnormal oxidative metabolism in the cuprizone mouse model of demyelination an in vivo nirs mri study |
| topic | Cuprizone mouse model Demyelination Cerebral metabolic rate of oxygen Cytochrome C oxidase NIRS MRI |
| url | http://www.sciencedirect.com/science/article/pii/S1053811922000647 |
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