Brain, Vol. 124, No. 6, 1114-1124,
June 2001
© 2001 Oxford University Press
Distribution of a calcium channel subunit in dystrophic axons in multiple sclerosis and experimental autoimmune encephalomyelitis
1 Department of Neuroimmunology, Brain Research Institute and 2 Department of Neurology, University of Vienna, 3 Department of Neurology, Hospital Lainz, Vienna, 4 Department of Neurology, Karl-Franzens-University, Graz, Austria, 5 Neuroimmunology Unit, Center of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden and 6 Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Martinsried, Germany
Correspondence to:
Professor Dr Hans Lassmann, Division of Neuroimmunology, Brain Research Institute, University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria E-mail: hans.lassmann{at}univie.ac.at
Multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) are immune-mediated diseases of the CNS. They are characterized by widespread inflammation, demyelination and a variable degree of axonal loss. Recent magnetic resonance spectroscopy studies have indicated that axonal damage and loss are a reliable correlate of permanent clinical disability. Accordingly, neuropathological studies have confirmed the presence and timing of axonal injury in multiple sclerosis lesions. The mechanisms of axonal degeneration, however, are unclear. Since calcium influx may mediate axonal damage, we have studied the distribution of the pore-forming subunit of neuronal (N)-type voltage-gated calcium channels in the lesions of multiple sclerosis and EAE. We found that 
1B, the pore-forming subunit of N-type calcium channels, was accumulated within axons and axonal spheroids of actively demyelinating lesions. The axonal staining pattern of 1B was comparable with that of ß-amyloid precursor protein, which is an early and sensitive marker for disturbance of axonal transport. Importantly, within these injured axons, 1B was not only accumulated, but also integrated in the axoplasmic membrane, as shown by immune electron microscopy on the EAE material. This ectopic distribution of calcium channels in the axonal membrane may result in increased calcium influx, contributing to axonal degeneration, possibly via the activation of neutral proteases. Our data suggest that calcium influx through voltage-dependent calcium channels is one possible candidate mechanism for axonal degeneration in inflammatory demyelinating disorders.
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