Sex-Differences in Traumatic Brain Injury in the Absence of Tau in Drosophila

Traumatic brain injuries, a leading cause of death and disability worldwide, are caused by a severe impact to the head that impairs physiological and psychological function. In addition to severity, type and brain area affected, brain injury outcome is also influenced by the biological sex of the patient. Traumatic brain injury triggers accumulation of Tau protein and the subsequent development of Tauopathies, including Alzheimer’s disease and Chronic traumatic encephalopathy. Recent studies report differences in Tau network connections between healthy males and females, but the possible role of Tau in sex-dependent outcome to brain injury is unclear. Thus, we aimed to determine if Tau ablation would alleviate sex dependent outcomes in injured flies. We first assessed motor function and survival in tau knock-out flies and observed sex-differences in climbing ability, but no change in locomotor activity in either sex post-injury. Sex differences in survival time were also observed in injured tau deficient flies with a dramatically higher percent of female death within 24 h than males. Additionally, 3′mRNA-Seq studies in isolated fly brains found that tau deficient males show more gene transcript changes than females post-injury. Our results suggest that sex differences in TBI outcome and recovery are not dependent on the presence of Tau in Drosophila.