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The Journal of Neuroscience, October 15, 1999, 19(20):8979-8989
Bovine CNS Myelin Contains Neurite Growth-Inhibitory Activity
Associated with Chondroitin Sulfate Proteoglycans
Barbara P.
Niederöst1,
Dieter R.
Zimmermann2,
Martin E.
Schwab1, and
Christine E.
Bandtlow1
1 Brain Research Institute, University of Zürich
and Swiss Federal Institute of Technology, Zürich,
Winterthurerstrasse 190, CH-8057 Zürich, Switzerland, and
2 Molecular Biology Laboratory, Department of Pathology,
University Hospital, Schmelzbergstrasse 12, CH-8091 Zürich,
Switzerland
The absence of fiber regrowth in the injured mammalian CNS
is influenced by several different factors and mechanisms. Besides the
nonconducive properties of the glial scar tissue that forms around the
lesion site, individual molecules present in CNS myelin and expressed
by oligodendrocytes, such as NI-35/NI-250, bNI-220, and
myelin-associated glycoprotein (MAG), have been isolated and shown to
inhibit axonal growth. Here, we report an additional neurite
growth-inhibitory activity purified from bovine spinal cord myelin that
is not related to bNI-220 or MAG. This activity can be ascribed to the
presence of two chondroitin sulfate proteoglycans (CSPGs), brevican and
the brain-specific versican V2 splice variant. Neurite outgrowth of
neonatal cerebellar granule cells and of dorsal root ganglion neurons
in vitro was strongly inhibited by this myelin fraction
enriched in CSPGs. Immunohistochemical staining revealed that brevican
and versican V2 are present on the surfaces of differentiated
oligodendrocytes. We provide evidence that treatment of
oligodendrocytes with the proteoglycan synthesis inhibitors -xylosides can strongly influence the growth permissiveness of oligodendrocytes. -Xylosides abolished cell surface presentation of
brevican and versican V2 and reversed growth cone collapse in
encounters with oligodendrocytes as demonstrated by time-lapse video
microscopy. Instead, growth cones were able to grow along or even into
the processes of oligodendrocytes. Our results strongly suggest that
brevican and versican V2 are additional components of CNS myelin that
contribute to its nonpermissive substrate properties for axonal growth.
Expression of these CSPGs on oligodendrocytes may indicate that they
participate in the restriction of structural plasticity and
regeneration in the adult CNS.
Key words:
neurite growth inhibition; CNS myelin; chondroitin
sulfate proteoglycans; oligodendrocyte; regeneration; spinal cord
Copyright © 1999 Society for Neuroscience 0270-6474/99/19208979-11$05.00/0
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