Sensory neuron-specific sodium channel SNS is abnormally expressed in the brains of mice with experimental allergic encephalomyelitis and humans withmultiple sclerosis

Clinical abnormalities in multiple sclerosis (MS) have classically been con sidered to be caused by demyelination and/or axonal degeneration; the possi bility of molecular changes in neurons, such as the deployment of abnormal repertoires of ion channels that would alter neuronal electrogenic properti es, has not been considered. Sensory Neuron-Specific sodium channel SNS dis plays a depolarized voltage dependence, slower activation and inactivation kinetics, and more rapid recovery from inactivation than classical "fast" s odium channels. SNS is selectively expressed in spinal sensory and trigemin al ganglion neurons within the peripheral nervous system and is not express ed within the normal brain. Here we show that sodium channel SNS mRNA and p rotein, which are not present within the cerebellum of control mice, are ex pressed within cerebellar Purkinje cells in a mouse model of MS, chronic re lapsing experimental allergic encephalomyelitis. We also demonstrate SNS mR NA and protein expression within Purkinje cells from tissue obtained postmo rtem from patients with MS, but not in control subjects with no neurologica l disease. These results demonstrate a change in sodium channel expression in neurons within the brain in an animal model of MS and in humans with MS and suggest that abnormal patterns of neuronal ion channel expression may c ontribute to clinical abnormalities such as ataxia in these disorders.