Professor Universidad Nacional Autónoma de México Mexico, United States
Abstract: The brain of axolotls regenerate in few weeks after tissue damage. In this study, we analyzed the early molecular changes by analyzing transcriptomic, miRNA and proteomic profiles within the first 6 hours, in the surrounding brain tissue, after partial removal of the dorsal pallium in wild-type animals from Mexico City. We identified a rapid activation of genes related to neural development, immune response, and tissue repair. Among the differentially expressed genes, key regeneration-associated genes and transcription factors were up-regulated, suggesting a swift molecular response conducive to neural regeneration. Proteomic analysis supported these findings, with early upregulation of proteins involved in cytoskeleton dynamics and synapse reorganization. miRNA analysis revealed downregulation of specific miRNAs, such as miR-199a-5p, correlating with the upregulation of regeneration-related genes. Cell-type enrichment bioinformatic analysis highlighted the involvement of ependymoglial cells in early post-injury events. The mechanical brain lesions made in this work are similar to the traumatic brain injury (TBI), which in mammals often causes tissue damage that leads to irreversible conditions of disability, due its limited regenerative capacity. A comparative analysis between axolotl and human TBI datasets underscored the unique regenerative pathways in axolotls, but also allowed the identification of 39 differentially expressed genes coincident in both species, offering insights that could aid to the development of future therapeutic strategies for enhancing neural repair in humans.
Funding Source: This work was supported by Conacyt-Tubitak 255793; additional support for I.V. laboratory includes PAPIIT-UNAM IN219122 and Pew Innovation Fund Biomed Innovation 2022-A-22568.
