Using Drosophila as an integrated model to study mild repetitive traumatic brain injury.
Using Drosophila as an integrated model to study mild repetitive traumatic brain injury.
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DOI：
10.1038/srep25252
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发表时间：
2016-05-04
影响因子：
4.6
通讯作者：
Ratliff EP
中科院分区：
文献类型：
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作者：
Barekat A;Gonzalez A;Mauntz RE;Kotzebue RW;Molina B;El-Mecharrafie N;Conner CJ;Garza S;Melkani GC;Joiner WJ;Lipinski MM;Finley KD;Ratliff EP
创伤性脑损伤（TBI）是全球发病率和死亡率的主要原因。此外，人们越来越认识到，即使是重复性的、较轻微的创伤性脑损伤（mTBI）形式也会对神经组织产生长期的有害影响。阻碍我们理解影响损伤的细胞和分子反应的遗传和环境因素的是，可用于识别调节创伤性脑损伤的急性和长期反应的关键基因和途径的有效遗传模型系统有限。在此，我们报告了一种使用果蝇建立的重度和轻度重复性创伤性脑损伤模型。利用该系统，在果蝇中也发现了哺乳动物创伤性脑损伤模型中常见的关键特征，包括炎症和自噬反应的激活、Tau蛋白磷酸化增加以及损害睡眠相关行为的神经元缺陷。这种新的损伤模式证明了果蝇作为一种有效工具的实用性，可用于验证影响整个动物对创伤反应的遗传和环境因素，并确定治疗创伤性脑损伤所需的潜在疗法。
Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. In addition, there has been a growing appreciation that even repetitive, milder forms of TBI (mTBI) can have long-term deleterious consequences to neural tissues. Hampering our understanding of genetic and environmental factors that influence the cellular and molecular responses to injury has been the limited availability of effective genetic model systems that could be used to identify the key genes and pathways that modulate both the acute and long-term responses to TBI. Here we report the development of a severe and mild-repetitive TBI model using Drosophila. Using this system, key features that are typically found in mammalian TBI models were also identified in flies, including the activation of inflammatory and autophagy responses, increased Tau phosphorylation and neuronal defects that impair sleep-related behaviors. This novel injury paradigm demonstrates the utility of Drosophila as an effective tool to validate genetic and environmental factors that influence the whole animal response to trauma and to identify prospective therapies needed for the treatment of TBI.