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

Ekta J Shah,Douglas M Ruden,Katherine Gurdziel

doi:10.3390/genes12060917

Abstract

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.

Highlights

Traumatic brain injury (TBI) is an insult to the brain from an external mechanical force, leading to permanent or temporary impairment of cognitive, physical and motor functions [1]
We looked at changes in transcript levels of genes involved in the Toll pathway which controls the transcription of the anti-fungal peptide Drosomycin (Drs) and the Imd pathway which activates the transcription of the anti-bacterial peptides Diptericin (Dpt), Cecropin [41] and Attacin (Att) [42] after injury in both sexes of tau-KO flies
We evaluated sex differences in TBI response in Drosophila inflicted with full body trauma in the absence of Tau

Summary

Introduction

Traumatic brain injury (TBI) is an insult to the brain from an external mechanical force, leading to permanent or temporary impairment of cognitive, physical and motor functions [1]. TBI causes physical injury to brain tissues that initiate molecular cascades involving unregulated neurotransmitter and ion release, inflammatory cytokines, altered gene transcription, apoptosis and free radical production [1]. Development of most Tauopathies is sporadic, brain injury can initiate misfolding and aggregation of Tau [2,3]. Tau, a protein encoded in humans by MAPT (microtubule associated protein Tau) gene, provides cytoskeletal support and promotes microtubule stability, dynamics and axonal transport processes [3]. Pathological Tau destabilizes the microtubule structure leading to axonal injury and damaged cytoskeleton, a common feature of brain injury [2,3]

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