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The Journal of Neuroscience, March 15, 2000, 20(6):2275-2286
Application of Neutralizing Antibodies against NI-35/250
Myelin-Associated Neurite Growth Inhibitory Proteins to the Adult
Rat Cerebellum Induces Sprouting of Uninjured Purkinje Cell
Axons
Annalisa
Buffo1,
Marta
Zagrebelsky1,
Andrea B.
Huber2,
Arne
Skerra3,
Martin E.
Schwab2,
Piergiorgio
Strata1, and
Ferdinando
Rossi1
1 Department of Neuroscience and "Rita Levi
Montalcini Center for Brain Repair," University of Turin, I-10125
Turin, Italy, 2 Brain Research Institute, University of
Zurich, and Federal Institute of Technology, CH-8057 Zurich,
Switzerland, and 3 Lehrstuhl für Biologische Chemie,
Technische Universität München, D-85350 München,
Germany
The myelin-associated proteins NI-35/250 exert a powerful
inhibition on axon regeneration, but their function exerted on intact neurons is still unclear. In the adult CNS these proteins are thought
to regulate axon growth processes to confine plasticity within
restricted regions and to prevent the formation of aberrant connections. We have recently shown that application of neutralizing IN-1 antibody Fab fragment against NI-35/250 proteins to the adult cerebellum induces the expression of injury/growth-associated markers
in intact Purkinje cells. Here, we asked whether these cellular
modifications are accompanied by growth phenomena of Purkinje neurites.
A single intraparenchymal application of IN-1 Fab fragment to the adult
cerebellum induces a profuse sprouting of Purkinje axons along their
intracortical course. The newly formed processes spread to cover most
of the granular layer depth. A significant axon outgrowth is evident
2 d after injection; it tends to increase at 5 and 7 d, but
it is almost completely reversed after 1 month. No axonal modifications
occur in control Fab-treated cerebella. The IN-1 Fab fragment-induced
cellular changes and axon remodeling are essentially reproduced by
applying affinity-purified antibody 472 raised against a peptide
sequence of the recombinant protein NI-220, thus confirming the
specificity of the applied treatments on these myelin-associated
molecules. Functional neutralization of NI-35/250 proteins induces
outgrowth from uninjured Purkinje neurites in the adult cerebellum.
Together with previous observations, this suggests that these molecules
regulate axonal plasticity to maintain the proper targeting of terminal
arbors within specific gray matter regions.
Key words:
sprouting; myelin-associated neurite growth inhibitors; axon growth-associated proteins; axon regeneration; intrinsic
determinants; cerebellum
Copyright © 2000 Society for Neuroscience 0270-6474/00/2062275-12$05.00/0
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