Exp Brain Res. 2004 Apr 29
Saab CY, Craner MJ, Kataoka Y, Waxman SG.
Department of Neurology and PVA/EPVA Center for Neuroscience Research, Yale University School of Medicine, New Haven, CT, USA.
Cerebellar deficits in multiple sclerosis (MS) tend to persist and can produce significant disability.
Although the pathophysiological basis for these deficits is not clear, it was recently reported that the expression of the sensory neuron-specific sodium channel Na(v)1.8 (which is not normally expressed within the cerebellum) is aberrantly upregulated within Purkinje cells in experimental allergic encephalomyelitis (EAE) and in human MS.
The expression of Na(v)1.8 in cultured Purkinje cells has been shown to alter the activity pattern of these cells in vitro by decreasing the number of spikes per conglomerate action potential and by contributing to the production of sustained, pacemaker-like activity upon depolarization, suggesting the hypothesis that, in pathophysiological situations where Na(v)1.8 is upregulated within Purkinje cells, the pattern of activity in these cells will be altered.
In the present study, we examined this hypothesis in vivo in mice with EAE.
Our results demonstrate a reduction in the number of secondary spikes per complex spike and irregularity in the temporal organization of secondary spikes in Purkinje cells from mice with EAE in which Na(v)1.8 is upregulated.
We also observed abnormal bursting activity in Purkinje cells from mice with EAE, which was not observed in control animals.
These results demonstrate functional changes in Purkinje cells in vivo within their native cerebellar environment in EAE, a model of MS, and support the hypothesis that misexpression of Na(v)1.8 can contribute to cerebellar deficits in neuroinflammatory disorders by altering the pattern of electrical activity within the cerebellum.