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

• Type of Material: Article
• Authors: Changtian Ye, Emory University; Joseph A Behnke, Emory University; Katherine R Hardin, Emory University; James Zheng, Emory University
• Language: English
• Date: 2023-04-03
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2023 Ye, Behnke, Hardin and Zheng.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fnins.2023.1150694
• Title of Journal or Parent Work: FRONTIERS IN NEUROSCIENCE
• Volume: 17
• Start Page: 1150694
• End Page: 1150694
• Grant/Funding Information: This work is supported in part by research grants from National Institutes of Health to JZ (GM083889 and MH129019), a Pilot grant to JZ from the NIH-funded Emory Specialized Center of Research Excellence in Sex Differences (U54AG062334), a Diana Jacobs Kalman Scholarship from American Federation for Aging Research (AFAR) to CY, and a T32 training grant from National Institute of General Medicine to Emory BCDB program (1T32GM135060-01).
• Keywords: SYSTEMATIC NOMENCLATURE; STEROID-HORMONES; risk factors; Science & Technology; INNATE IMMUNE-RESPONSE; SPONTANEOUS LOCOMOTOR-ACTIVITY; Neurosciences & Neurology; OXIDATIVE STRESS; neurodegeneration; aging; traumatic brain injury; Neurosciences; INSULIN-RECEPTOR; COGNITIVE IMPAIRMENT; LIFE-SPAN; Life Sciences & Biomedicine; sex difference; RISK-FACTOR; ALZHEIMER-DISEASE
• Research Categories: Biology, Cell

Abstract

Repetitive physical insults to the head, including those that elicit mild traumatic brain injury (mTBI), are a known risk factor for a variety of neurodegenerative conditions including Alzheimer’s disease (AD), Parkinson’s disease (PD), and chronic traumatic encephalopathy (CTE). Although most individuals who sustain mTBI typically achieve a seemingly full recovery within a few weeks, a subset experience delayed-onset symptoms later in life. As most mTBI research has focused on the acute phase of injury, there is an incomplete understanding of mechanisms related to the late-life emergence of neurodegeneration after early exposure to mild head trauma. The recent adoption of Drosophila-based brain injury models provides several unique advantages over existing preclinical animal models, including a tractable framework amenable to high-throughput assays and short relative lifespan conducive to lifelong mechanistic investigation. The use of flies also provides an opportunity to investigate important risk factors associated with neurodegenerative conditions, specifically age and sex. In this review, we survey current literature that examines age and sex as contributing factors to head trauma-mediated neurodegeneration in humans and preclinical models, including mammalian and Drosophila models. We discuss similarities and disparities between human and fly in aging, sex differences, and pathophysiology. Finally, we highlight Drosophila as an effective tool for investigating mechanisms underlying head trauma-induced neurodegeneration and for identifying therapeutic targets for treatment and recovery.