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Abnormal Purkinje cell activity in vivo in experimental allergic encephalomyelitis

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Abstract

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 Nav1.8 (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 Nav1.8 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 Nav1.8 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 Nav1.8 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 Nav1.8 can contribute to cerebellar deficits in neuroinflammatory disorders by altering the pattern of electrical activity within the cerebellum.

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Acknowledgements

We thank Dr. Albert Lo for his advice on the EAE model. The study was supported in part by grants from the National Multiple Sclerosis Society and the Medical Research Service and Rehabilitation Research Service, Department of Veterans Affairs. We also thank the Paralyzed Veterans of America, the Eastern Paralyzed Veterans Association, the Nancy Davis Foundation, and Destination Cure for support.

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Authors and Affiliations

  1. Department of Neurology and PVA/EPVA Center for Neuroscience Research, Yale University School of Medicine, New Haven, CT, USA

    Carl Y. Saab, Matthew J. Craner, Yuko Kataoka & Stephen G. Waxman

  2. Rehabilitation Research Center, VA Connecticut Healthcare System, West Haven, CT, USA

    Carl Y. Saab, Matthew J. Craner, Yuko Kataoka & Stephen G. Waxman

  3. Department of Neurology, LCI-707, Yale University School of Medicine, 333 Cedar Street, PO Box 208018, New Haven, CT 06520-8018, USA

    Stephen G. Waxman

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  1. Carl Y. Saab
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Correspondence to Stephen G. Waxman.

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Saab, C.Y., Craner, M.J., Kataoka, Y. et al. Abnormal Purkinje cell activity in vivo in experimental allergic encephalomyelitis. Exp Brain Res 158, 1–8 (2004). https://doi.org/10.1007/s00221-004-1867-4

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