J Neuropathol Exp Neurol. 2003 Sep;62(9):968-75
Craner MJ, Kataoka Y, Lo AC, Black JA, Baker D, Waxman SG.
Department of Neurology and PVA/EPVA Center for Neuroscience Research, Yale University School of Medicine, New Haven, Connecticut 06520-8018, USA.
Multiple sclerosis (MS) is recognized to involve demyelination and axonal atrophy but accumulating evidence suggests that dysregulated sodium channel expression may also contribute to its pathophysiology.
Recent studies have demonstrated that the expression of Na(v)1.8 voltage-gated sodium channels, which are normally undetectable within the CNS, is upregulated in cerebellar Purkinje cells in experimental allergic encephalomyelitis (EAE) and MS, and suggest that the aberrant expression of these channels contributes to clinical dysfunction by distorting the firing pattern of these neurons.
In this study we examined the temporal pattern of upregulation for Na(v)1.8 mRNA and protein in chronic relapsing EAE by in situ hybridization and immunocytochemistry, respectively.
Our results demonstrate a positive correlation between disease duration and degree of upregulation of Na(v)1.8 mRNA and protein in Purkinje neurons in chronic-relapsing EAE.
The progressive deterioration in clinical baseline scores (i.e. in clinical scores during remissions) is paralleled by a continued increase in Na(v)1.8 mRNA and protein expression, but temporary worsening during relapses is not associated with transient changes in Na(v)1.8 expression.
These results provide evidence that the expression of sodium channel Na(v)1.8 contributes to the development of clinical deficits in an in vivo model of neuroinflammatory disease.