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Sadeghian, M, Mastrolia, V, Rezaei Haddad, A, Mosley, A, Mullali, G, Schiza, D, Sajic, M, Hargreaves, IP, Heales, S, Duchen, MR and Smith, KJ (2016) Mitochondrial dysfunction is an important cause of neurological deficits in an inflammatory model of multiple sclerosis. Scientific Reports, 6 (1). ISSN 2045-2322
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Abstract
Neuroinflammation can cause major neurological dysfunction, without demyelination, in both multiplesclerosis (MS) and a mouse model of the disease (experimental autoimmune encephalomyelitis; EAE), but the mechanisms remain obscure. Confocal in vivo imaging of the mouse EAE spinal cord reveals that impaired neurological function correlates with the depolarisation of both the axonal mitochondria and the axons themselves. Indeed, the depolarisation parallels the expression of neurological deficit at the onset of disease, and during relapse, improving during remission in conjunction with the deficit. Mitochondrial dysfunction, fragmentation and impaired trafficking were most severe in regions of extravasated perivascular inflammatory cells. The dysfunction at disease onset was accompanied by increased expression of the rate-limiting glycolytic enzyme phosphofructokinase-2 in activated astrocytes, and by selective reduction in spinal mitochondrial complex I activity. The metabolic changes preceded any demyelination or axonal degeneration. We conclude that mitochondrial dysfunction is a major cause of reversible neurological deficits in neuroinflammatory disease, such as MS.
| Item Type: | Article |
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| Subjects: | R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Pharmacy & Biomolecular Sciences |
| Publisher: | Nature Research |
| Date Deposited: | 02 Apr 2019 10:07 |
| Last Modified: | 04 Sep 2021 02:40 |
| DOI or ID number: | 10.1038/srep33249 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/8741 |
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