The cell neural adhesion molecule contactin-2 (TAG-1) is beneficial for functional recovery after spinal cord injury in adult zebrafish

• Published in: PloS one 2012-12, Vol.7 (12), p.e52376-e52376
• Main Authors: Lin, Jin-Fei, Pan, Hong-Chao, Ma, Li-Ping, Shen, Yan-Qin, Schachner, Melitta
• Format: Article
• Language: English
• Subjects: Adhesion; Aging - metabolism; Analysis; Animals; Anterograde transport; Antisense RNA; Axons; Axons - metabolism; Axons - pathology; Biology; Brain; Cell adhesion & migration; Collaboration; Contactin; Contactin 2 - genetics; Contactin 2 - metabolism; Danio rerio; Extracellular matrix; Gene Knockdown Techniques; Genes; Hybridization; Immunofluorescence; Immunoglobulins; Injuries; Injury analysis; Islet-1 protein; Localization; Locomotion; Medicine; Motor Neurons - metabolism; Motor Neurons - pathology; mRNA; Myelination; Nervous system; Neurogenesis; Neurons; Neurosciences; Recovery; Recovery (Medical); Recovery of Function; Regeneration; Regrowth; Retrograde transport; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Spinal cord; Spinal cord injuries; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - pathology; Spinal Cord Injuries - physiopathology; Spinal cord injury; Swimming; Systems development; Time Factors; Trauma; Up-Regulation - genetics; Zebrafish; Zebrafish - metabolism; Zebrafish Proteins - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0052376

The cell neural adhesion molecule contactin-2 plays a key role in axon extension and guidance, fasciculation, and myelination during development. We thus asked, whether contactin-2 is also important in nervous system regeneration after trauma. In this study, we used an adult zebrafish spinal cord transection model to test the functions of contactin-2 in spinal cord regeneration. The expression patterns of contactin-2 at different time points after spinal cord injury were studied at the mRNA level by qPCR and in situ hybridization, and contactin-2 protein levels and immunohistological localization were detected by Western blot and immunofluorescence analyses, respectively. Contactin-2 mRNA and protein levels were increased along the central canal at 6 days and 11 days after spinal cord injury, suggesting a requirement for contactin-2 in spinal cord regeneration. Co-localization of contactin-2 and islet-1 (a motoneuron marker) was observed in spinal cords before and after injury. To further explore the functions of contactin-2 in regeneration, an anti-sense morpholino was used to knock down the expression of contactin-2 protein by application at the time of injury. Motion analysis showed that inhibition of contactin-2 retarded the recovery of swimming functions when compared to standard control morpholino. Anterograde and retrograde tracing at 6 weeks after injury showed that knock down of contactin-2 inhibited axonal regrowth from NMLF neurons beyond lesion site. The combined observations indicate that contactin-2 contributes to locomotor recovery and successful regrowth of axons after spinal cord injury in adult zebrafish.