Dietary restriction ameliorates TBI-induced phenotypes in Drosophila melanogaster.
Dietary restriction ameliorates TBI-induced phenotypes in Drosophila melanogaster.
复制标题
DOI：
10.1038/s41598-022-13128-x
复制
发表时间：
2022-06-09
影响因子：
4.6
通讯作者：
Shirasu-Hiza, Mimi M.
中科院分区：
文献类型：
--
作者：
Delventhal, Rebecca;Wooder, Emily R.;Basturk, Maylis;Sattar, Mohima;Lai, Jonathan;Bolton, Danielle;Muthukumar, Gayathri;Ulgherait, Matthew;Shirasu-Hiza, Mimi M.
创伤性脑损伤（TBI）每年影响数百万人，并与长期健康下降有关。TBI还与神经退行性疾病（ND）具有共同的分子和细胞特征，通常随着年龄的增长而增加患病率，并且是以后生活中发生神经退行性疾病的主要风险因素。虽然我们对特定ND中神经毒性的基因和途径的理解已经取得了进展，但我们仍然缺乏对驱动神经变性的早期分子和生理变化的完整理解，特别是随着TBI后个体年龄的增长。最近，果蝇被引入作为研究闭头TBI的模式生物。在本文中，我们提供了一个TBI苍蝇在成年早期，然后测量分子和生理表型在短期，中期和长期的时间点损伤后。我们的目标是确定导致神经退行性变的变化的时间。在这里，我们证实了先前的工作，证明了TBI诱导的寿命下降，并提出了运动功能进行性下降，强烈的急性和中度慢性神经炎症以及蛋白质聚集迟发性增加的证据。我们还提供了代谢功能障碍的证据，以饥饿敏感性和脂质降低的形式存在，这种情况持续超过即时损伤反应，但长期没有差异。饮食限制（DR）的干预部分改善了一些TBI诱导的表型，包括寿命和运动功能，但它不会改变受伤的苍蝇的饥饿敏感性的模式。在未来，TBI后被确定为改变的分子途径-特别是在短期或中期-可能是潜在的治疗靶点。
Traumatic brain injury (TBI) affects millions annually and is associated with long-term health decline. TBI also shares molecular and cellular hallmarks with neurodegenerative diseases (NDs), typically increasing in prevalence with age, and is a major risk factor for developing neurodegeneration later in life. While our understanding of genes and pathways that underlie neurotoxicity in specific NDs has advanced, we still lack a complete understanding of early molecular and physiological changes that drive neurodegeneration, particularly as an individual ages following a TBI. Recently Drosophila has been introduced as a model organism for studying closed-head TBI. In this paper, we deliver a TBI to flies early in adult life, and then measure molecular and physiological phenotypes at short-, mid-, and long-term timepoints following the injury. We aim to identify the timing of changes that contribute to neurodegeneration. Here we confirm prior work demonstrating a TBI-induced decline in lifespan, and present evidence of a progressive decline in locomotor function, robust acute and modest chronic neuroinflammation, and a late-onset increase in protein aggregation. We also present evidence of metabolic dysfunction, in the form of starvation sensitivity and decreased lipids, that persists beyond the immediate injury response, but does not differ long-term. An intervention of dietary restriction (DR) partially ameliorates some TBI-induced phenotypes, including lifespan and locomotor function, though it does not alter the pattern of starvation sensitivity of injured flies. In the future, molecular pathways identified as altered following TBI—particularly in the short-, or mid-term—could present potential therapeutic targets.
登录
查看更多内容
影响因子：
4.6
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
通讯作者：
Ratliff EP
影响因子：
5.2
作者：
Antosh, Michael;Fox, David;Neretti, Nicola
通讯作者：
Neretti, Nicola
影响因子：
13.3
作者：
Bartlett, Bryan J.;Isakson, Pauline;Finley, Kim D.
通讯作者：
Finley, Kim D.
影响因子：
7.8
作者：
Burger, Joep M. S.;Hwangbo, Dae Sung;Promislow, Daniel E. L.
通讯作者：
Promislow, Daniel E. L.
影响因子：
7.8
作者：
Bross, TG;Rogina, B;Helfand, SL
通讯作者：
Helfand, SL