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The Journal of Neuroscience, March 1, 2002, 22(5):1726-1737
Genetic Dysmyelination Alters the Molecular Architecture of the
Nodal Region
Edgardo J.
Arroyo1,
Theodore
Xu1,
Judith
Grinspan2,
Stephen
Lambert3,
S. Rock
Levinson4,
Peter J.
Brophy5,
Elior
Peles6, and
Steven S.
Scherer1
1 Department of Neurology, The University of
Pennsylvania Medical Center and 2 Division of Neurology
Research, Children's Hospital of Philadelphia, Philadelphia,
Pennsylvania 19104-6077, 3 Program in Neuroscience,
University of Massachusetts Medical Center, Worcester, Massachusetts
01605, 4 Department of Physiology, University of Colorado
Health Science Center, Denver, Colorado 80262, 5 Department
of Preclinical Veterinary Sciences, University of Edinburgh,
Summerhall, Edinburgh EH9 1QH, United Kingdom, and
6 Department of Molecular Cell Biology, Weizmann Institute
of Science, 76100 Rehovot, Israel
We have examined the molecular organization of axons in the spinal
cords of myelin-deficient (md) rats,
which have profound CNS dysmyelination associated with oligodendrocyte
cell death. Although myelin sheaths are rare, most large axons are at
least partially surrounded by oligodendrocyte processes. At postnatal day 7 (P7), almost all node-like clusters of voltage-gated
Na+ channels and ankyrinG are adjacent
to axonal segments ensheathed by oligodendrocytes, but at P21, many
node-like clusters are found in axonal segments that lack
oligodendrocyte ensheathment. In P21 wild-type (WT) rats, the
voltage-gated Na+ channels Nav1.2,
Nav1.6, and Nav1.8, are found in different
subpopulations of myelinated axons, and md rats have a
similar distribution. The known molecular components of
paranodes contactin, Caspr, and neurofascin 155are not clustered in
md spinal cords, and no septate-like junctions between
oligodendrocyte processes and axons are found by electron microscopy.
Furthermore, Kv1.1 and Kv1.2 K+ channels are not
spatially segregated from the node-like clusters of
Na+ channels in md rats, in contrast
to their WT littermates. These results suggest the following: node-like
clusters of voltage-gated Na+ channels and
ankyrinG form adjacent to ensheathed axonal segments even
in the absence of a myelin sheath; these clusters persist after
oligodendrocyte cell death; dysmyelination does not alter the
expression of different nodal of voltage-gated Na+
channels; the absence of paranodes results in the mislocalization of
neurofascin155, contactin, and Caspr, and the aberrant localization of
Kv1.1 and Kv1.2.
Key words:
myelin; oligodendrocytes; mutant; septate junctions; axon-glia interactions; proteolipid protein
Copyright © 2002 Society for Neuroscience 0270-6474/02/2251726-12$05.00/0
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