Brain Advance Access originally published online on June 9, 2006
Brain 2006 129(12):3186-3195; doi:10.1093/brain/awl144
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nodal, paranodal and juxtaparanodal axonal proteins during demyelination and remyelination in multiple sclerosis
1 INSERM U711 Paris, France 2 Université Pierre & Marie Curie (UPMC Paris 6) Paris, France 3 AP-HP, Hôpital de la Salpêtrière, Fédération des maladies du système nerveux Paris, France 4 Laboratoire de Neuropathologie IFR-70 Paris, France 5 INSERM U536 Paris, France 6 Department of Cellular and Molecular Neuroscience, Imperial College London London, UK
Correspondence to: Catherine Lubetzki, Biologie des Interactions Neurone-Glie, INSERM U711; Hôpital de la Salpêtrière, 47 Bd de l'Hôpital, 75651 Paris Cedex13, France E-mail: catherine.lubetzki{at}psl.ap-hop-paris.fr
Saltatory conduction in myelinated fibres depends on the specific molecular organization of highly specialized axonal domains at the node of Ranvier, the paranodal and the juxtaparanodal regions. Voltage-gated sodium channels (Nav) have been shown to be deployed along the naked demyelinated axon in experimental models of CNS demyelination and in multiple sclerosis lesions. Little is known about aggregation of nodal, paranodal and juxtaparanodal constituents during the repair process. We analysed by immunohistochemistry on free-floating sections from multiple sclerosis brains the expression and distribution of nodal (Nav channels), paranodal (paranodin/Caspr) and juxtaparanodal (Kv channels and Caspr2) molecules in demyelinated and remyelinated lesions. Whereas in demyelinated lesions, paranodal and juxtaparanodal proteins are diffusely distributed on denuded axons, the distribution of Nav channels is heterogeneous, with a diffuse immunoreactivity but also few broad Nav channel aggregates in all demyelinated lesions. In contrast to the demyelinated plaques, all remyelinated lesions are characterized by the detection of aggregates of Nav channels, paranodin/Caspr, Kv channels and Caspr2. Our data suggest that these aggregates precede remyelination, and that Nav channel aggregation is the initial event, followed by aggregation of paranodal and then juxtaparanodal axonal proteins. Remyelination takes place in multiple sclerosis tissue but myelin repair is often incomplete, and the reasons for this remyelination deficit are many. We suggest that a defect of Nav channel aggregation might be involved in the remyelination failure in demyelinated lesions with spared axons and oligodendroglial cells.
Key Words: multiple sclerosis; demyelination; remyelination; sodium channels; potassium channels
Abbreviations: ALS, amyotrophic lateral sclerosis; MBP, myelin basic protein; Nav, voltage-gated sodium channels; PBS, phosphate-buffered saline; PLP, proteolipid protein
Received February 3, 2006. Revised April 9, 2006. Accepted May 5, 2006.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Bachelin, V. Zujovic, D. Buchet, J. Mallet, and A. Baron-Van Evercooren Ectopic expression of polysialylated neural cell adhesion molecule in adult macaque Schwann cells promotes their migration and remyelination potential in the central nervous system Brain, October 20, 2009; (2009) awp256v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dubois-Dalcq, A. Williams, C. Stadelmann, B. Stankoff, B. Zalc, and C. Lubetzki From fish to man: understanding endogenous remyelination in central nervous system demyelinating diseases Brain, July 1, 2008; 131(7): 1686 - 1700. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Susuki and M. N. Rasband Spectrin and Ankyrin-Based Cytoskeletons at Polarized Domains in Myelinated Axons Exp Biol Med, April 1, 2008; 233(4): 394 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. K. Mathey, T. Derfuss, M. K. Storch, K. R. Williams, K. Hales, D. R. Woolley, A. Al-Hayani, S. N. Davies, M. N. Rasband, T. Olsson, et al. Neurofascin as a novel target for autoantibody-mediated axonal injury J. Exp. Med., October 1, 2007; 204(10): 2363 - 2372. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Herrero-Herranz, L. A. Pardo, G. Bunt, R. Gold, W. Stuhmer, and R. A. Linker Re-Expression of a Developmentally Restricted Potassium Channel in Autoimmune Demyelination: Kv1.4 Is Implicated in Oligodendroglial Proliferation Am. J. Pathol., August 1, 2007; 171(2): 589 - 598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Smith Axonal protection in multiple sclerosis--a particular need during remyelination? Brain, December 1, 2006; 129(12): 3147 - 3149. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Simons and K. Trajkovic Neuron-glia communication in the control of oligodendrocyte function and myelin biogenesis J. Cell Sci., November 1, 2006; 119(21): 4381 - 4389. [Abstract] [Full Text] [PDF]
|
|