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Increased mitochondrial content in remyelinated axons: implications for multiple sclerosis

Zambonin, Jessica L ; Zhao, Chao ; Ohno, Nobuhiko ; Campbell, Graham R ; Engeham, Sarah ; Ziabreva, Iryna ; Schwarz, Nadine ; Lee, Sok Ee ; Frischer, Josa M ; Turnbull, Doug M ; Trapp, Bruce D ; Lassmann, Hans ; Franklin, Robin J. M ; Mahad, Don J

Brain (London, England : 1878), 2011-07, Vol.134 (7), p.1901-1913 [Periódico revisado por pares]

Oxford: Oxford University Press

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Título:
Increased mitochondrial content in remyelinated axons: implications for multiple sclerosis
Autor: Zambonin, Jessica L ; Zhao, Chao ; Ohno, Nobuhiko ; Campbell, Graham R ; Engeham, Sarah ; Ziabreva, Iryna ; Schwarz, Nadine ; Lee, Sok Ee ; Frischer, Josa M ; Turnbull, Doug M ; Trapp, Bruce D ; Lassmann, Hans ; Franklin, Robin J. M ; Mahad, Don J
Assuntos: Adult ; Aged ; Aged, 80 and over ; Animals ; Antigens, CD - metabolism ; Antigens, Differentiation, Myelomonocytic - metabolism ; Axons - metabolism ; Axons - pathology ; Axons - ultrastructure ; Biological and medical sciences ; Brain - metabolism ; Brain - pathology ; Brain - ultrastructure ; Cells, Cultured ; Coculture Techniques ; Demyelinating Diseases - chemically induced ; Disease Models, Animal ; Ethidium - toxicity ; Female ; Ganglia, Spinal - drug effects ; HLA Antigens - metabolism ; Humans ; Leukocyte Common Antigens - metabolism ; Lysophosphatidylcholines - toxicity ; Male ; Medical sciences ; Microscopy, Electron, Transmission ; Middle Aged ; Mitochondria - drug effects ; Mitochondria - metabolism ; Multiple Sclerosis - pathology ; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis ; Myelin Basic Protein - metabolism ; Neurofilament Proteins - metabolism ; Neurology ; Original ; Rats ; Rats, Sprague-Dawley ; Schwann Cells - drug effects ; Voltage-Dependent Anion Channels - metabolism
É parte de: Brain (London, England : 1878), 2011-07, Vol.134 (7), p.1901-1913
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
Descrição: Mitochondrial content within axons increases following demyelination in the central nervous system, presumably as a response to the changes in energy needs of axons imposed by redistribution of sodium channels. Myelin sheaths can be restored in demyelinated axons and remyelination in some multiple sclerosis lesions is extensive, while in others it is incomplete or absent. The effects of remyelination on axonal mitochondrial content in multiple sclerosis, particularly whether remyelination completely reverses the mitochondrial changes that follow demyelination, are currently unknown. In this study, we analysed axonal mitochondria within demyelinated, remyelinated and myelinated axons in post-mortem tissue from patients with multiple sclerosis and controls, as well as in experimental models of demyelination and remyelination, in vivo and in vitro. Immunofluorescent labelling of mitochondria (porin, a voltage-dependent anion channel expressed on all mitochondria) and axons (neurofilament), and ultrastructural imaging showed that in both multiple sclerosis and experimental demyelination, mitochondrial content within remyelinated axons was significantly less than in acutely and chronically demyelinated axons but more numerous than in myelinated axons. The greater mitochondrial content within remyelinated, compared with myelinated, axons was due to an increase in density of porin elements whereas increase in size accounted for the change observed in demyelinated axons. The increase in mitochondrial content in remyelinated axons was associated with an increase in mitochondrial respiratory chain complex IV activity. In vitro studies showed a significant increase in the number of stationary mitochondria in remyelinated compared with myelinated and demyelinated axons. The number of mobile mitochondria in remyelinated axons did not significantly differ from myelinated axons, although significantly greater than in demyelinated axons. Our neuropathological data and findings in experimental demyelination and remyelination in vivo and in vitro are consistent with a partial amelioration of the supposed increase in energy demand of demyelinated axons by remyelination.
Editor: Oxford: Oxford University Press
Idioma: Inglês

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Increased mitochondrial content in remyelinated axons: implications for multiple sclerosis

Zambonin, Jessica L ; Zhao, Chao ; Ohno, Nobuhiko ; Campbell, Graham R ; Engeham, Sarah ; Ziabreva, Iryna ; Schwarz, Nadine ; Lee, Sok Ee ; Frischer, Josa M ; Turnbull, Doug M ; Trapp, Bruce D ; Lassmann, Hans ; Franklin, Robin J. M ; Mahad, Don J

Oxford: Oxford University Press

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