Title: Understanding Spinal Cord Injury in Zebrafish: Chemical and Genetic Methods for CNS Studies

Abstract: Spinal cord injuries (SCIs) are devastating because the initial injury triggers a self-propagating cascade of biochemical mechanisms leading to additional tissue loss and permanent dysfunction. Reagents that promote functional recovery could provide new hope for patients, and animal models that are capable of regeneration are our best resource for discovering such factors. The zebrafish central nervous system (CNS) shares many organizational, cellular and molecular pathways with mammals; however, functional regeneration occurs in zebrafish even after complete transection of the spinal cord. Unfortunately, our understanding of how the CNS of zebrafish responds to injury and subsequently regenerates remains incomplete.

The Mruk laboratory’s long-term goal is to elucidate the molecular basis governing CNS regeneration. Understanding how the zebrafish CNS deals with SCI offers a unique opportunity to tap into this question. Data mining previously published transcriptional datasets and our own preliminary data has identified differential regulation of ion channels after SCI. Our overall hypothesis is that electrical signaling between innate immune cells and glia dictate the extent of functional recovery observed in the zebrafish after SCI. We will use a combination of imaging, genetic lines, and behavioral assays to study how the electrical network is changing, which ions channels contribute to this change, and whether the changes in electricity contribute to functional recovery after SCI. This project has broad impacts as the tools and lines we develop will advance our ability to identify new therapeutic approaches to attenuate inflammation and promote recovery as well as study disease pathology and facilitate drug screening to identify new therapeutics for neurodegenerative diseases.