The past and present of Drosophila models of traumatic brain injury

Drosophila melanogaster as a model to study age and sex differences in brain injury and neurodegeneration after mild head trauma

“…Perhaps most impressive of the inherent Drosophila toolbox is the genetically tractable nature of fruit flies, which is unparalleled by any mammalian system. Many transgenic models of specific neurodegenerative diseases have been generated to study the progression of neurodegeneration, such as AD ( Prüßing et al, 2013 ), PD ( Whitworth, 2011 ), FTD ( West, 2015 ), HD ( Krench and Littleton, 2013 ), ALS ( Casci and Pandey, 2015 ), and CTE ( Aggarwal et al, 2022 ; Figure 1A ). The ability to systematically probe protein function and control transgene expression in a cell-specific manner enables interrogation of various signaling mechanisms and opportunities for high-throughput screens.…”

“…A summary of different Drosophila TBI models and the key findings from research using these models is provided in Supplementary Table 1 . These models have also been extensively covered by other reviews ( Shah et al, 2019 ; Buhlman et al, 2021 ; Aggarwal et al, 2022 ). It should be noted that studies using Drosophila TBI models have recapitulated several key aspects of trauma found in humans and other preclinical models of trauma, including acute stress responses such as oxidative stress and lysosomal activity, progressive neurodegeneration, neuronal hyperexcitability, and glial-specific responses ( Barekat et al, 2016 ; Sun and Chen, 2017 ; Saikumar et al, 2020 ; Behnke et al, 2021 ; Saikumar et al, 2021 ; van Alphen et al, 2022 ).…”