Guedes Vivian A, Lai Chen, Devoto Christina, Edwards Katie A, Mithani Sara, Sass Dilorom, Vorn Rany, Qu Bao-Xi, Rusch Heather L, Martin Carina A, Walker William C, Wilde Elisabeth A, Diaz-Arrastia Ramon, Gill Jessica M, Kenney Kimbra
Tissue Injury Branch, National Institutes of Nursing Research, National Institutes of Health, Bethesda, MD, United States.
Center for Neuroscience and Regenerative Medicine, Uniformed Services University, Bethesda, MD, United States.
Front Pharmacol. 2021 Oct 6;12:745348. doi: 10.3389/fphar.2021.745348. eCollection 2021.
Symptoms of post-traumatic stress disorder (PTSD) are common in military populations, and frequently associated with a history of combat-related mild traumatic brain injury (mTBI). In this study, we examined relationships between severity of PTSD symptoms and levels of extracellular vesicle (EV) proteins and miRNAs measured in the peripheral blood in a cohort of military service members and Veterans (SMs/Vs) with chronic mTBI(s). Participants ( = 144) were divided into groups according to mTBI history and severity of PTSD symptoms on the PTSD Checklist for DSM-5 (PCL-5). We analyzed EV levels of 798 miRNAs (miRNAs) as well as EV and plasma levels of neurofilament light chain (NfL), Tau, Amyloid beta (Aβ) 42, Aβ40, interleukin (IL)-10, IL-6, tumor necrosis factor-alpha (TNFα), and vascular endothelial growth factor (VEGF). We observed that EV levels of neurofilament light chain (NfL) were elevated in participants with more severe PTSD symptoms (PCL-5 ≥ 38) and positive mTBI history, when compared to TBI negative controls ( = 0.024) and mTBI participants with less severe PTSD symptoms ( = 0.006). Levels of EV NfL, plasma NfL, and hsa-miR-139-5p were linked to PCL-5 scores in regression models. Our results suggest that levels of NfL, a marker of axonal damage, are associated with PTSD symptom severity in participants with remote mTBI. Specific miRNAs previously linked to neurodegenerative and inflammatory processes, and glucocorticoid receptor signaling pathways, among others, were also associated with the severity of PTSD symptoms. Our findings provide insights into possible signaling pathways linked to the development of persistent PTSD symptoms after TBI and biological mechanisms underlying susceptibility to PTSD.
创伤后应激障碍（PTSD）的症状在军人中很常见，并且经常与战斗相关的轻度创伤性脑损伤（mTBI）病史有关。在本研究中，我们在一组患有慢性mTBI的军人和退伍军人（SMs/Vs）中，研究了PTSD症状的严重程度与外周血中细胞外囊泡（EV）蛋白和miRNA水平之间的关系。参与者（n = 144）根据mTBI病史和DSM-5创伤后应激障碍检查表（PCL-5）上PTSD症状的严重程度进行分组。我们分析了798种miRNA的EV水平，以及神经丝轻链（NfL）、Tau、淀粉样β蛋白（Aβ）42、Aβ40、白细胞介素（IL）-10、IL-6、肿瘤坏死因子-α（TNFα）和血管内皮生长因子（VEGF）的EV和血浆水平。我们观察到，与TBI阴性对照组（p = 0.024）和PTSD症状较轻的mTBI参与者相比，PTSD症状较严重（PCL-5≥38）且有阳性mTBI病史的参与者中，神经丝轻链（NfL）的EV水平升高（p = 0.006）。在回归模型中，EV NfL、血浆NfL和hsa-miR-139-5p的水平与PCL-5评分相关。我们的结果表明，轴突损伤标志物NfL的水平与远期mTBI参与者的PTSD症状严重程度相关。先前与神经退行性和炎症过程以及糖皮质激素受体信号通路等相关的特定miRNA，也与PTSD症状的严重程度相关。我们的研究结果为TBI后持续性PTSD症状发展相关的可能信号通路以及PTSD易感性的生物学机制提供了见解。
