Major vault protein promotes locomotor recovery and regeneration after spinal cord injury in adult zebrafish

• Published in: The European journal of neuroscience 2013-01, Vol.37 (2), p.203-211
• Main Authors: Pan, Hong-Chao, Lin, Jin-Fei, Ma, Li-Ping, Shen, Yan-Qin, Schachner, Melitta
• Format: Article
• Language: English
• Subjects: Animals; Axons - metabolism; Axons - physiology; Biological and medical sciences; Development. Senescence. Regeneration. Transplantation; Ependyma - cytology; Fundamental and applied biological sciences. Psychology; Intermediate Filament Proteins - genetics; Intermediate Filament Proteins - metabolism; LIM-Homeodomain Proteins - genetics; LIM-Homeodomain Proteins - metabolism; Locomotion; major vault protein; Morpholinos; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nestin; neural stem cell; regeneration; RNA, Messenger - biosynthesis; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - physiopathology; spinal cord injury; Spinal Cord Regeneration; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Tyrosine 3-Monooxygenase - genetics; Tyrosine 3-Monooxygenase - metabolism; Vault Ribonucleoprotein Particles - genetics; Vault Ribonucleoprotein Particles - metabolism; Vertebrates: nervous system and sense organs; Zebrafish
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.12038

In contrast to mammals, adult zebrafish recover locomotor functions after spinal cord injury (SCI), in part due to axonal regrowth and regeneration permissivity of the central nervous system. Upregulation of major vault protein (MVP) expression after spinal cord injury in the brainstem of the adult zebrafish prompted us to probe for its contribution to recovery after SCI. MVP is a multifunctional protein expressed not only in many types of tumours but also in the nervous system, where its importance for regeneration is, however, unclear. Using an established zebrafish SCI model, we found that MVP mRNA and protein expression levels were increased in ependymal cells in the spinal cord caudal to the lesion site at 6 and 11 days after SCI. Double immunolabelling showed that MVP was co‐localised with Islet‐1 or tyrosine hydroxylase around the central canal of the spinal cord in sham‐injured control fish and injured fish 11 days after surgery. MVP co‐localised with the neural stem cell marker nestin in ependymal cells after injury. By using an in vivo morpholino‐based knock‐down approach, we found that the distance moved by MVP morpholino‐treated fish was reduced at 4, 5 and 6 weeks after SCI when compared to fish treated with standard control morpholino. Knock‐down of MVP resulted in reduced regrowth of axons from brainstem neurons into the spinal cord caudal to the lesion site. These results indicate that MVP supports locomotor recovery and axonal regrowth after SCI in adult zebrafish. MVP expression levels increased in the spinal cord caudal to the lesion site after spinal cord injury (SCI) in adult zebrafish. Inhibition of MVP by morpholino in vivo impairs recovery of locomotor functions of zebrafish and results in reduced regrowth of axons from the brain. These findings indicate that MVP is an essential regulator of regeneration after SCI and that it may be a potential target for therapy of acute central nervous system lesions.