Mitochondrial dysfunction is an important cause of neurological deficits in an inflammatory model of multiple sclerosis

Scientific Reports

Volumn 6, Issue , 2016, Pages

  Sadeghian, Mona ^a   Mastrolia, Vincenzo ^a   Rezaei Haddad, Ali ^a   Mosley, Angelina ^a   Mullali, Gizem ^a   Schiza, Dimitra ^a   Sajic, Marija ^a   Hargreaves, Iain ^b   Heales, Simon ^c   Duchen, Michael R ^d   Smith, Kenneth J ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b NATIONAL HOSPITAL FOR NEUROLOGY AND NEUROSURGERY   (United Kingdom)

^c GREAT ORMOND STREET HOSPITAL   (United Kingdom)

^d UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

6 PHOSPHOFRUCTO 2 KINASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE);

ANIMAL; AXON; DISEASE MODEL; ENZYMOLOGY; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; GENETICS; HUMAN; INFLAMMATION; METABOLISM; MITOCHONDRION; MOUSE; MULTIPLE SCLEROSIS; NEUROLOGIC DISEASE; PATHOLOGY; SPINAL CORD;

ANIMALS; AXONS; DISEASE MODELS, ANIMAL; ELECTRON TRANSPORT COMPLEX I; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; HUMANS; INFLAMMATION; MICE; MITOCHONDRIA; MULTIPLE SCLEROSIS; NERVOUS SYSTEM DISEASES; PHOSPHOFRUCTOKINASE-2; SPINAL CORD;

EID: 84987811630     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep33249     Document Type: Article

References (42)

1. Nikic, I. et al. A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat. Med. 17, 495-499 (2011).
2. McDonald, W. I., Sears, T. A. The effects of experimental demyelination on conduction in the central nervous system. Brain 93, 583-598 (1970).
3. Youl, B. D. et al. Destructive lesions in demyelinating disease. J. Neurol. Neurosurg. Psychiatry 54, 288-292 (1991).
4. Moreau, T. et al. Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis. Brain 119, 225-237 (1996).
5. Bitsch, A. et al. Lesion development in Marburg's type of acute multiple sclerosis: From inflammation to demyelination. Multiple Sclerosis 5, 138-146 (1999).
6. Hedegaard, C. J. et al. T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis. Immunology 125, 161-169 (2008).
7. Redford, E. J., Kapoor, R., Smith, K. J. Nitric oxide donors reversibly block axonal conduction: demyelinated axons are especially susceptible. Brain 120, 2149-2157 (1997).
8. Shrager, P., Custer, A. W., Kazarinova, K., Rasband, M. N., Mattson, D. Nerve conduction block by nitric oxide that is mediated by the axonal environment. J. Neurophysiol. 79, 529-536 (1998).
9. Smith, K. J., Kapoor, R., Hall, S. M., Davies, M. Electrically active axons degenerate when exposed to nitric oxide. Ann. Neurol. 49, 470-476 (2001).
10. Murphy, M. P. How mitochondria produce reactive oxygen species. Biochem. J 417, 1-13 (2009).
11. Lu, F. et al. Oxidative damage to mitochondrial DNA and activity of mitochondrial enzymes in chronic active lesions of multiple sclerosis. J. neurol. Sci. 177, 95-103 (2000).
12. Dutta, R. et al. Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann. Neurol. 59, 478-489 (2006).
13. Ciccarelli, O. et al. Assessing neuronal metabolism in vivo by modeling imaging measures. J. Neurosci. 30, 15030-15033 (2010).
14. Narayanan, S. et al. Axonal metabolic recovery in multiple sclerosis patients treated with interferon beta-1b. J. Neurol. 248, 979-986 (2001).
15. Vidaurre, O. G. et al. Cerebrospinal fluid ceramides from patients with multiple sclerosis impair neuronal bioenergetics. Brain 137, 2271-2286 (2014).
16. Aboul-Enein, F., Weiser, P., Hoftberger, R., Lassmann, H., Bradl, M. Transient axonal injury in the absence of demyelination: a correlate of clinical disease in acute experimental autoimmune encephalomyelitis. Acta Neuropathol. 111, 539-547 (2006).
17. Griffiths, I. et al. Axonal swellings and degeneration in mice lacking the major proteolipid of myelin. Science 280, 1610-1613 (1998).
18. Smith, K. J. Axonal protection in multiple sclerosis-a particular need during remyelination? Brain 129, 3147-3149 (2006).
19. Bostock, H., Sears, T. A. Continuous conduction in demyelinated mammalian nerve fibers. Nature 263, 786-787 (1976).
20. Smith, K. J., Bostock, H., Hall, S. M. Saltatory conduction precedes remyelination in axons demyelinated with lysophosphatidyl choline. J. neurol. Sci. 54, 13-31 (1982).
21. Felts, P. A., Baker, T. A., Smith, K. J. Conduction in segmentally demyelinated mammalian central axons. J. Neurosci. 17, 7267-7277 (1997).
22. Nicholls, D. G. Mitochondrial function and dysfunction in the cell: its relevance to aging and aging-related disease. Int. J. Biochem. Cell Biol. 34, 1372-1381 (2002).
23. Qi, X., Lewin, A. S., Sun, L., Hauswirth, W. W., Guy, J. Mitochondrial protein nitration primes neurodegeneration in experimental autoimmune encephalomyelitis. J. Biol. Chem. 281, 31950-31962 (2006).
24. Hartung, H. P., Schafer, B., Heininger, K., Toyka, K. V. Suppression of experimental autoimmune neuritis by the oxygen radical scavengers superoxide dismutase and catalase. Ann. Neurol. 23, 453-460 (1988).
25. Choi, B. Y. et al. Inhibition of NADPH oxidase activation reduces EAE-induced white matter damage in mice. J. Neuroinflammation. 12, 104 (2015).
26. Cassina, A. M. et al. Cytochrome c nitration by peroxynitrite. J. Biol. Chem. 275, 21409-21415 (2000).
27. Brown, G. C., Borutaite, V. Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols. Biochim. Biophys. Acta 1658, 44-49 (2004).
28. Yamamoto, T. et al. Selective nitration of mitochondrial complex I by peroxynitrite: involvement in mitochondria dysfunction and cell death of dopaminergic SH-SY5Y cells. J. Neural Transm. 109, 1-13 (2002).
29. Davies, A. L. et al. Neurological deficits caused by tissue hypoxia in neuroinflammatory diseas. Ann. Neurol. 74, 815-825 (2013).
30. Cai, Q., Davis, M. L., Sheng, Z. H. Regulation of axonal mitochondrial transport and its impact on synaptic transmission. Neurosci. Res. 70, 9-15 (2011).
31. Ashrafi, G., Schlehe, J. S., LaVoie, M. J., Schwarz, T. L. Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin. J. Cell Biol. 206, 655-670 (2014).
32. Witte, M. E. et al. Enhanced number and activity of mitochondria in multiple sclerosis lesions. J Pathol. 219, 193-204 (2009).
33. Mahad, D., Lassmann, H., Turnbull, D. Review: Mitochondria and disease progression in multiple sclerosis. Neuropathol. Appl. Neurobiol. 34, 577-589 (2008).
34. Sorbara, C. D. et al. Pervasive axonal transport deficits in multiple sclerosis models. Neuron 84, 1183-1190 (2014).
35. Chang, D. T., Reynolds, I. J. Mitochondrial trafficking and morphology in healthy and injured neurons. Prog. Neurobiol. 80, 241-268 (2006).
36. Centonze, D. et al. The link between inflammation, synaptic transmission and neurodegeneration in multiple sclerosis. Cell Death. Differ. 17, 1083-1091 (2010).
37. Wegner, C., Esiri, M. M., Chance, S. A., Palace, J., Matthews, P. M. Neocortical neuronal, synaptic, and glial loss in multiple sclerosis. Neurology 67, 960-967 (2006).
38. Sharma, R. et al. Inflammation induced by innate immunity in the central nervous system leads to primary astrocyte dysfunction followed by demyelination. Acta Neuropathol. 120, 223-236 (2010).
39. Wolburg-Buchholz, K. et al. Loss of astrocyte polarity marks blood-brain barrier impairment during experimental autoimmune encephalomyelitis. Acta Neuropathol. 118, 219-233 (2009).
40. Pilkis, S. J., Claus, T. H., Kurland, I. J., Lange, A. J. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: a metabolic signaling enzyme. Annu. Rev. Biochem. 64, 799-835 (1995).
41. Almeida, A., Almeida, J., Bolanos, J. P., Moncada, S. Different responses of astrocytes and neurons to nitric oxide: the role of glycolytically generated ATP in astrocyte protection. Proc. Natl. Acad. Sci. USA 98, 15294-15299 (2001).
42. Sajic, M. et al. Impulse conduction increases mitochondrial transport in adult mammalian peripheral nerves in vivo. PLoS. Biol. 11, e1001754 (2013).