Abstract No.: | C-C3099 |
Country: | Canada |
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Title: | FIBROBLASTS ARE A MAJOR SOURCE OF NETRIN-1 IN THE INJURED MOUSE SPINAL CORD |
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Authors/Affiliations: | 2 K. Adam Baker*; 2 Sarah-Jane Bull; 1 Sam David; 2 Timothy Kennedy;
1 Montreal General Hospital; 2 Montreal Neurological Institute; QC, Canada
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Content: | Objectives: Netrin-1 is a bifunctional chemotropic guidance cue, attracting some axons and repelling others. UNC5 homologue netrin receptors are required for the repellant response. UNC5 homologues are the predominant netrin-1 receptors expressed by neurons in the mature spinal cord supporting the conclusion that netrin-1 may function as a myelin associated inhibitor of axon regeneration. Recent reports have presented apparently conflicting findings, in one case concluding that netrin-1 expression is upregulated in the adult mouse CNS following injury, while in the other demonstrating that netrin-1 expression in the adult rat spinal cord at a site of injury remained below control levels. Here we sought to clarify these results by examining the consequences of spinal cord injury in mice that carry a LacZ reporter gene under the transcriptional control of the endogenous netrin-1 promoter.
Material and Methods: Cervical dorsal hemisections were performed in transgenic mice and expression of β-gal at the injury site assessed 8 days following injury. Expression of β-gal in mixed glial cultures derived from netrin-1 transgenic mice was also investigated.
Results: Increased netrin-1 expression was detected in the glial scar 8 days post-injury. Immunohistochemical double labeling detected netrin-1 expression by fibroblasts and a subset of astrocytes but not microglia/macrophages. Results consistent with these findings were also obtained in vitro.
Conclusion: These results provide evidence that netrin-1 is expressed at sites of injury in the adult mouse CNS. The difference between this and previous findings in the rat spinal cord suggest that injury-induced expression of netrin-1 may exhibit species-specific characteristics.
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