Hehar Harleen, Mychasiuk Richelle
Alberta Children's Hospital Research Foundation, University of Calgary, Faculty of Medicine, Calgary, AB, Canada.
Alberta Children's Hospital Research Foundation, University of Calgary, Faculty of Medicine, Calgary, AB, Canada.
Neurobiol Dis. 2016 Mar;87:11-8. doi: 10.1016/j.nbd.2015.12.007. Epub 2015 Dec 17.
Telomeres were originally believed to be passive players in cellular replication, but recent research has highlighted their more active role in epigenetic patterning and promotion of cellular growth and survival. Furthermore, literature demonstrates that telomere length (TL) is responsive to environmental manipulations such as prenatal stress and dietary programming. As the search for a prognostic biomarker of concussion has had limited success, this study sought to examine whether or not telomere length (TL) could be an efficacious predictor of symptom severity in juvenile rats following concussion. Rats from four distinct experimental groups (caloric restriction (CR), high fat diet (HFD), exercise (EX), and standard controls (STD)) received a mild traumatic brain injury (mTBI)/concussion and were then subjected to a behavioural test battery. The test battery was scored and the animals were categorized as poor, average, or good, based on their performance on the 6 tests examined. Skin cells (from ear notch samples) were taken 17days post-injury and DNA was extracted for telomere length analysis. Ear notch skin cell TL was highly correlated with brain tissue TL for a given individual. Animals in the CR and EX cohorts had significantly longer telomeres, while animals in the HFD cohort had significantly shorter telomeres, when compared to controls. The mTBI/concussion reduced TL in all cohorts except the EX group. A significant linear relationship was found between TL and performance on the behavioural test battery, whereby shorter telomeres were associated with poorer performance and longer telomeres with better performance. As performance on the test battery is linked to symptom severity, this study found TL to be a reasonable tool for concussion prognosis. Future studies with human populations should examine the validity of TL in peripheral cells, as a predictor of concussion pathology.
端粒最初被认为是细胞复制中的被动参与者，但最近的研究突出了它们在表观遗传模式以及促进细胞生长和存活方面更积极的作用。此外，文献表明端粒长度（TL）对诸如产前应激和饮食编程等环境操纵有反应。由于寻找脑震荡预后生物标志物的研究取得的成功有限，本研究旨在探讨端粒长度（TL）是否可以作为幼鼠脑震荡后症状严重程度的有效预测指标。来自四个不同实验组（热量限制（CR）、高脂饮食（HFD）、运动（EX）和标准对照组（STD））的大鼠接受轻度创伤性脑损伤（mTBI）/脑震荡，然后进行一系列行为测试。对测试进行评分，并根据它们在所检查的6项测试中的表现将动物分为差、中或好三类。在受伤后17天采集皮肤细胞（来自耳部切口样本）并提取DNA用于端粒长度分析。对于给定个体，耳部切口皮肤细胞的TL与脑组织的TL高度相关。与对照组相比，CR和EX组的动物端粒明显更长，而HFD组的动物端粒明显更短。mTBI/脑震荡使除EX组外的所有组的TL缩短。在TL与行为测试的表现之间发现了显著的线性关系，即端粒越短，表现越差，端粒越长，表现越好。由于测试的表现与症状严重程度相关，本研究发现TL是脑震荡预后的合理工具。未来针对人群的研究应检验外周细胞中TL作为脑震荡病理学预测指标的有效性。
