Dissecting the Molecular Signature of Spinal Cord Regeneration in the Axolotl Model

Abstract

Thousands of people are affected by central nervous system (CNS) dysfunctions each year, with stroke and spinal cord injury (SCI) being the most frequent causes. Although there is some evidence of partial CNS self-repair (via migration of neural stem cells to the injury zone and adult neurogenesis), due to restricted regeneration capacity in mammals, acute or chronic spinal cord injuries cannot be repaired completely. Therefore, to expand the availability of treatment options for SCI, research on highly regenerative animals has become essential. Among vertebrates, axolotl, a salamander species, has been emerging as a powerful model to explore the molecular mechanisms of regeneration due to its exceptional regenerative capacity. In this study, gene expression modulation for regenerative-capable neotenic axolotl during spinal cord regeneration has been investigated. Next-generation sequencing was applied for the collected regeneration samples at zero and seven days post-amputation (dpa). The data obtained from the analyzed samples revealed 363 genes differentially expressed, mostly downregulated, between zero dpa and seven dpa. The extracellular matrix, cell-cell adhesion, and immune system-related processes and pathways were enriched by gene ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Based on these data, we conclude that the downregulation of immune system-related biological processes is crucial for spinal cord regeneration.