Loss of highwire protects against the deleterious effects of traumatic brain injury in Drosophila Melanogaster

Abstract BackgroundTraumatic brain injury (TBI) is a major global cause of death and disability. Axonal injury is a major underlying mechanism of TBI and could represent a major therapeutic target. We provide evidence that targeting the axonal death pathway known as Wallerian degeneration (WD) improves outcome in a Drosophila Melanogaster model of high impact trauma. This cell-autonomous neurodegenerative pathway is initiated following axon injury, and in Drosophila, involves activity of the E3 ubiquitin ligase highwire. In this study we explore the effects of that a loss-of-function mutation in the highwire gene has on a range of outcomes following high impact trauma.ResultsResults demonstrate that a loss-of-function mutation in the highwire gene rescues deleterious effects of a traumatic injury, including - improved functional outcomes including climbing ability and flight maintenance, lifespan, survival of a subset of dopaminergic neurons, and retention of synaptic proteins.ConclusionWe demonstrate that a loss-of-function mutation in the highwire gene rescues deleterious effects of a traumatic injury. This data suggests that highwire represents a potential therapeutic target in traumatic injury.