Assessment of Mitochondrial Dysfunction in Experimental Autoimmune Encephalomyelitis (EAE) Models of Multiple Sclerosis
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that involves the autoreactive T-cell attack on axonal myelin sheath. Lesions or plaques formed as a result of repeated damage and repair mechanisms lead to impaired relay of electrical impulses alon...
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doaj-b030ee8e38e047c0b8b579f192561a452020-11-25T02:50:06ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-10-012020497510.3390/ijms20204975ijms20204975Assessment of Mitochondrial Dysfunction in Experimental Autoimmune Encephalomyelitis (EAE) Models of Multiple SclerosisXiulin Ng0Mona Sadeghian1Simon Heales2Iain P. Hargreaves3UCL Institute of Neurology, Queen Square, University College London, London WC1N 3BG, UKDepartment of Neuroinflammation, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, London WC1N 3BG, UKDepartment of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UKDepartment of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UKMultiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that involves the autoreactive T-cell attack on axonal myelin sheath. Lesions or plaques formed as a result of repeated damage and repair mechanisms lead to impaired relay of electrical impulses along the nerve, manifesting as clinical symptoms of MS. Evidence from studies in experimental autoimmune encephalomyelitis (EAE) models of MS strongly suggests that mitochondrial dysfunction presents at the onset of disease and throughout the disease course. The aim of this study was to determine if mitochondrial dysfunction occurs before clinical symptoms arise, and whether this is confined to the CNS. EAE was induced in C57B/L6 mice, and citrate synthase and mitochondrial respiratory chain (MRC) complex I−IV activities were assayed at presymptomatic (3 or 10 days post first immunisation (3 or 10 DPI)) and asymptomatic (17 days post first immunisation (17 DPI) time-points in central nervous system (CNS; spinal cord) and peripheral (liver and jaw muscle) tissues. Samples from animals immunised with myelin oligodendrocyte glycoprotein (MOG) as EAE models were compared with control animals immunised with adjuvant (ADJ) only. Significant changes in MOG compared to control ADJ animals in MRC complex I activity occurred only at presymptomatic stages, with an increase in the spinal cord at 10 DPI (87.9%), an increase at 3 DPI (25.6%) and decrease at 10 DPI (22.3%) in the jaw muscle, and an increase in the liver at 10 DPI (71.5%). MRC complex II/III activity changes occurred at presymptomatic and the asymptomatic stages of the disease, with a decrease occurring in the spinal cord at 3 DPI (87.6%) and an increase at 17 DPI (36.7%), increase in the jaw muscle at 10 DPI (25.4%), and an increase at 3 DPI (75.2%) and decrease at 17 DPI (95.7%) in the liver. Citrate synthase activity was also significantly decreased at 10 DPI (27.3%) in the liver. No significant changes were observed in complex IV across all three tissues assayed. Our findings reveal evidence that mitochondrial dysfunction is present at the asymptomatic stages in the EAE model of MS, and that the changes in MRC enzyme activities are tissue-specific and are not confined to the CNS.https://www.mdpi.com/1422-0067/20/20/4975multiple sclerosismitochondrial dysfunctionexperimental autoimmune encephalomyelitisfatigue and weakness |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiulin Ng Mona Sadeghian Simon Heales Iain P. Hargreaves |
spellingShingle |
Xiulin Ng Mona Sadeghian Simon Heales Iain P. Hargreaves Assessment of Mitochondrial Dysfunction in Experimental Autoimmune Encephalomyelitis (EAE) Models of Multiple Sclerosis International Journal of Molecular Sciences multiple sclerosis mitochondrial dysfunction experimental autoimmune encephalomyelitis fatigue and weakness |
author_facet |
Xiulin Ng Mona Sadeghian Simon Heales Iain P. Hargreaves |
author_sort |
Xiulin Ng |
title |
Assessment of Mitochondrial Dysfunction in Experimental Autoimmune Encephalomyelitis (EAE) Models of Multiple Sclerosis |
title_short |
Assessment of Mitochondrial Dysfunction in Experimental Autoimmune Encephalomyelitis (EAE) Models of Multiple Sclerosis |
title_full |
Assessment of Mitochondrial Dysfunction in Experimental Autoimmune Encephalomyelitis (EAE) Models of Multiple Sclerosis |
title_fullStr |
Assessment of Mitochondrial Dysfunction in Experimental Autoimmune Encephalomyelitis (EAE) Models of Multiple Sclerosis |
title_full_unstemmed |
Assessment of Mitochondrial Dysfunction in Experimental Autoimmune Encephalomyelitis (EAE) Models of Multiple Sclerosis |
title_sort |
assessment of mitochondrial dysfunction in experimental autoimmune encephalomyelitis (eae) models of multiple sclerosis |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-10-01 |
description |
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that involves the autoreactive T-cell attack on axonal myelin sheath. Lesions or plaques formed as a result of repeated damage and repair mechanisms lead to impaired relay of electrical impulses along the nerve, manifesting as clinical symptoms of MS. Evidence from studies in experimental autoimmune encephalomyelitis (EAE) models of MS strongly suggests that mitochondrial dysfunction presents at the onset of disease and throughout the disease course. The aim of this study was to determine if mitochondrial dysfunction occurs before clinical symptoms arise, and whether this is confined to the CNS. EAE was induced in C57B/L6 mice, and citrate synthase and mitochondrial respiratory chain (MRC) complex I−IV activities were assayed at presymptomatic (3 or 10 days post first immunisation (3 or 10 DPI)) and asymptomatic (17 days post first immunisation (17 DPI) time-points in central nervous system (CNS; spinal cord) and peripheral (liver and jaw muscle) tissues. Samples from animals immunised with myelin oligodendrocyte glycoprotein (MOG) as EAE models were compared with control animals immunised with adjuvant (ADJ) only. Significant changes in MOG compared to control ADJ animals in MRC complex I activity occurred only at presymptomatic stages, with an increase in the spinal cord at 10 DPI (87.9%), an increase at 3 DPI (25.6%) and decrease at 10 DPI (22.3%) in the jaw muscle, and an increase in the liver at 10 DPI (71.5%). MRC complex II/III activity changes occurred at presymptomatic and the asymptomatic stages of the disease, with a decrease occurring in the spinal cord at 3 DPI (87.6%) and an increase at 17 DPI (36.7%), increase in the jaw muscle at 10 DPI (25.4%), and an increase at 3 DPI (75.2%) and decrease at 17 DPI (95.7%) in the liver. Citrate synthase activity was also significantly decreased at 10 DPI (27.3%) in the liver. No significant changes were observed in complex IV across all three tissues assayed. Our findings reveal evidence that mitochondrial dysfunction is present at the asymptomatic stages in the EAE model of MS, and that the changes in MRC enzyme activities are tissue-specific and are not confined to the CNS. |
topic |
multiple sclerosis mitochondrial dysfunction experimental autoimmune encephalomyelitis fatigue and weakness |
url |
https://www.mdpi.com/1422-0067/20/20/4975 |
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