Axonal expression of sodium channels and neuropathology of the plaques in multiple sclerosis
Version of Record online: 1 JUL 2014
© 2013 British Neuropathological Society
Neuropathology and Applied Neurobiology
Volume 40, Issue 5, pages 579–590, August 2014
How to Cite
Bouafia, A., Golmard, J.-L., Thuries, V., Sazdovitch, V., Hauw, J. J., Fontaine, B. and Seilhean, D. (2014), Axonal expression of sodium channels and neuropathology of the plaques in multiple sclerosis. Neuropathology and Applied Neurobiology, 40: 579–590. doi: 10.1111/nan.12059
- Issue online: 1 JUL 2014
- Version of Record online: 1 JUL 2014
- Accepted manuscript online: 10 MAY 2013 05:25AM EST
- Manuscript Revised: 10 MAY 2013
- Manuscript Accepted: 30 APR 2013
- Manuscript Received: 28 JUL 2012
- BrainNet Europe II
- active demyelinating;
- inactive not demyelinating;
- microglial hyperplasia;
- multiple sclerosis;
- sodium channels;
- T cells
Although demyelination is an important cause of neurological deficits in multiple sclerosis (MS), recently axonal pathology and concomitant involvement of sodium channels (Nav) became a focus of major interest. Studies in experimental autoimmune encephalomyelitis (EAE) and MS have shown diffuse expression of Nav1.6 and Nav1.2 along demyelinated axons. However, the relation between this expression by the axon and its environment is not yet known. The aim of this exploratory study was to identify the neuropathological characteristics of the plaque associated with the changes of sodium channel axonal expression.
We analysed by immunohistochemistry the expression of Nav1.6 and Nav1.2 along demyelinated axons in 64 plaques from 12 MS cases. To characterize the plaques, we used Luxol fast blue staining and immunohistochemistry for myelin basic protein, microglia/macrophages, T and B cells, reactive astrocytes and axonal lesions performed on sections of formalin-fixed, paraffin-embedded tissue.
The presence of diffuse axonal expression of Nav1.6 was equally distributed between active demyelinating and inactive not demyelinating plaques based on presence or absence of myelin laden macrophages respectively. However, presence of diffuse axonal expression of Nav1.6 was more frequent within plaques with T cells infiltrate and microglial hyperplasia. On the other hand, Nav1.2 diffuse axonal expression seemed to be independent of the neuropathological environment of the plaque.
The cellular environment of the axon influences the differential expression of Nav channels. A better understanding of the influence of the inflammation on sodium channels mediated axonal degeneration could offer therapeutic perspectives.