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.
Highlights
Spinal cord injury (SCI) is one of the more common acute central nervous system (CNS) injuries seen throughout the world
We explored the molecular mechanisms in spinal cord regeneration by utilizing the axolotl model
As shown in previous studies, for successful regeneration, the dedifferentiation of specialized cells, cell division, and cell migration processes provided by the reorganization of cell-cell and cell-extracellular matrix (ECM) adhesion capacity are required to facilitate the formation of blastema tissue [11,20]
Summary
Spinal cord injury (SCI) is one of the more common acute central nervous system (CNS) injuries seen throughout the world. Limited treatment options are available for spinal cord repair and regeneration [1]. The very quick physiological response to the acute injury following the initial damage is the restrictive point to the development of effective therapies for SCI, and medical interventions to prevent the effect of secondary injury is the typical approach to SCI treatment [3]. Functional consolidation of the CNS after an injury in some species such as zebrafish and salamanders has attracted the attention of researchers to decipher the regenerative capacity code in these animals [4]. The lack of a successful clinical therapy option for SCI cases promotes the usage of animal models to understand the molecular mechanisms involved in the course of spinal cord regeneration
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