Traumatic brain injury induced neurodegeneration in a Drosophila model Bounajem, M.T.1, Frost, B.2 1Joe R. & Teresa Lozano Long School of Medicine; 2Barshop Institute for Longevity and Aging Studies
Introduction: Traumatic brain injury (TBI) is a neurodegenerative disease believed to be a type of tauopathy, although the mechanism of TBI-induced neuronal damage has not been clearly delineated. The tau protein accumulation characteristic of tauopathies has recently been shown by Frost et al. to cause neurodegeneration via a process of lamin dysfunction, resultant heterochromatin relaxation, and ultimately neuronal apoptosis in a fly model. The reasoning therefore stands that if tau accumulation causes neuronal apoptosis, and TBI is a tauopathy, then TBI should cause neuronal apoptosis. In this study, we aim to show that TBI causes neurodegeneration via neuronal apoptosis in a Drosophila melanogaster model. Methods: TBI was induced in two-day old flies via the HIT device proposed by Katzenberger et al. Flies were loaded into a vial and attached to the end of a spring; the opposite end of the spring was in turn fastened to a horizontal wooden plank. The fly end was retracted to 90° and released. Flies received either one hit, two hits, or no hits (control). Flies were then aged to either 10 or 20 days, embedded in paraffin wax, and sectioned at four microns. Flies that died before the intended sacrifice day were excluded from analysis. Results: Apoptosis was assessed via a TUNEL assay. A one-way ANOVA was run to determine if the number of hits caused a significant difference in apoptosis between the three age-matched groups (n=6 per group). Among the flies aged to 10 days, there was no significant difference between the three groups (F=3.25, p>0.05). The 20-day flies also did not show outstanding differences between groups. Discussion: These findings suggest that neuronal apoptosis was not induced in flies using the HIT device, likely due to the variable nature of the injury. Moving forward, we intend to employ an injury mechanism that produces a more reliable head injury by delivering an impact directly to the fly head. Our goal is that by demonstrating the underlying pathophysiology of TBI, we may more accurately characterize TBI's relation to the other tauopathies.
Funding NIH, AFAR
Credits
Credits: None available.
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