The Journal of Neuroscience, May 3, 2006, 26(18):4729-4739; doi:10.1523/JNEUROSCI.3900-05.2006
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Development/Plasticity/Repair
Antibodies against the NG2 Proteoglycan Promote the Regeneration of Sensory Axons within the Dorsal Columns of the Spinal Cord
Andrew M. Tan,1
Mario Colletti,1
Ann T. Rorai,1
J. H. Pate Skene,2 and
Joel M. Levine1
1Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, New York 11794, and 2Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710
Correspondence should be addressed to Dr. Joel Levine, Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, NY 11794. Email: joel.levine{at}sunysb.edu
The NG2 chondroitin sulfate proteoglycan inhibits axon growth in vitro. Levels of NG2 increase rapidly in the glial scars that form at sites of CNS injury, suggesting that NG2 may inhibit axon regeneration. To determine the functions of NG2, we infused mixtures of neutralizing or non-neutralizing anti-NG2 monoclonal antibodies into the dorsally transected adult rat spinal cord and analyzed the regeneration of ascending mechanosensory axons anatomically. At 1 week after injury, ascending sensory axons in control animals terminated caudal to the lesion within an area containing dense deposits of NG2 immunoreactivity. In animals treated with the neutralizing anti-NG2 antibodies, labeled axons penetrated the caudal border of the lesion and grew into and beyond the lesion center. The low intrinsic growth capacity of adult neurons may also limit the ability of damaged axons to regenerate. To enhance growth, we combined antibody treatment with a peripheral nerve conditioning lesion. After a conditioning lesion and treatment with control, non-neutralizing antibodies, many sensory axons grew into the lesion core. These axons did not grow past the rostral border of the lesion; rather, they grew along the dorsal surface of the spinal cord and within any remaining pieces of the dorsal roots. In contrast, combining a peripheral nerve conditioning lesion with neutralizing anti-NG2 antibodies resulted in sensory axon regeneration past the glial scar and into the white matter rostral to the injury site. The combinatorial approach used here that neutralizes extrinsic inhibition and increases intrinsic growth results in anatomically correct axon regeneration, a prerequisite for functional recovery.
Key words: NG2; chondroitin sulfate proteoglycans; glial scar; regeneration; sensory axons; spinal cord injury
Received Sept. 14, 2005;
revised March 14, 2006;
accepted March 19, 2006.
Correspondence should be addressed to Dr. Joel Levine, Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, NY 11794. Email: joel.levine{at}sunysb.edu
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