| Abstrakt: |
Background: Previous work from our lab has described a model of motor nerve degeneration in hyperglycemic zebrafish larvae which resembles mammalian models of diabetic peripheral neuropathy (DPN). Here, we optimized the hyperglycemic‐induction protocol, characterized deficits in nerve structure and behavioral function, and then examined the regenerative potential following recovery from the hyperglycemic state. Results: In agreement with our previous work, hyperglycemia induced motor nerve degeneration and behavioral deficits. However, the optimized protocol initiated disruption of tight junctions within the blood‐nerve barrier, a phenotype apparent in mammalian models of DPN. Following a 10‐day recovery period, regeneration of motor nerve components was apparent, but behavioral deficits persisted. We next examined the effect of hyperglycemia on the musculoskeletal system and found subtle deficits in muscle that resolved following recovery, and robust deficits in the skeletal system which persisted following recovery. Conclusion: Here we optimized our previous model of hyperglycemia‐induced motor nerve degeneration to more closely align with that observed in mammalian models and then characterized the regenerative potential following recovery from hyperglycemia. Notably, we observed striking impairments to skeletal development, which underscores the global impact hyperglycemia has across systems, and provides a framework for elucidating molecular mechanisms responsible for regenerative events moving forward. Key Findings: These findings describe a novel model of motor nerve regeneration following hyperglycemic injury in zebrafish larvae.Hyperglycemia severely impairs vertebral development, which persists following recovery in zebrafish, suggesting potential impacts of gestational diabetes and childhood diabetes on skeletal development in humans.This work lays the groundwork for future small molecule drug screens to determine molecular pathways involved in peripheral motor nerve regeneration. [ABSTRACT FROM AUTHOR] |
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