Functional Axonal Regeneration through Astrocytic Scar Genetically Modified to Digest Chondroitin Sulfate Proteoglycans

Axotomized neurons within the damaged CNS are thought to be prevented from functional regeneration by inhibitory molecules such as chondroitin sulfate proteoglycans (CSPGs) and myelin-associated inhibitors. Here, we provide a transgenic test of the role of CSPGs in limiting regeneration, using the g...

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Bibliographic Details
Published in:The Journal of neuroscience 2007-02, Vol.27 (9), p.2176-2185
Main Authors: Cafferty, William B. J, Yang, Shih-Hung, Duffy, Philip J, Li, Shuxin, Strittmatter, Stephen M
Format: Article
Language:English
Subjects:
Animals
Astrocytes - enzymology
Axons - physiology
Chondroitin ABC Lyase - metabolism
Chondroitin Sulfate Proteoglycans - genetics
Chondroitin Sulfate Proteoglycans - metabolism
Cicatrix - physiopathology
Female
Forelimb
Male
Mice
Mice, Transgenic
Nerve Regeneration - genetics
Pain Measurement
Rhizotomy
Sensation - physiology
Skin - innervation
Spinal Cord Injuries - physiopathology
Thoracic Vertebrae
Up-Regulation
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Summary:Axotomized neurons within the damaged CNS are thought to be prevented from functional regeneration by inhibitory molecules such as chondroitin sulfate proteoglycans (CSPGs) and myelin-associated inhibitors. Here, we provide a transgenic test of the role of CSPGs in limiting regeneration, using the gfap promotor to express a CSPG-degrading enzyme chondroitinase ABC (ChABC) in astrocytes. Corticospinal axons extend within the lesion site, but not caudal to it, after dorsal hemisection in the transgenic mice. The presence of the gfap-ChABC transgene yields no significant improvement in motor function recovery in this model. In contrast, functionally significant sensory axon regeneration is observed after dorsal rhizotomy in transgenic mice. These transgenic studies confirm a local efficacy for reduced CSPG to enhance CNS axon growth after traumatic injury. CSPGs appear to function in a spatially distinct role from myelin inhibitors, implying that combination-based therapy will be especially advantageous for CNS injuries.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.5176-06.2007