Acute and Chronic Molecular Signatures and Associated Symptoms of Blast Exposure in Military Breachers
| Autor: | Hanga Galfalvy, Walter Carr, Zhaoyu Wang, Gregory A. Elder, Yongchao Ge, Fatemeh Haghighi, Stephen T. Ahlers, Matthew L LoPresti, Natalia Mendelev, Gary H. Kamimori, Caroline Wilson, Angela M. Yarnell |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 030506 rehabilitation Chemokine Time Factors Transcription Genetic Explosions blast overpressure 03 medical and health sciences 0302 clinical medicine Blast Injuries Gene expression Medicine Humans Epigenetics sleep tinnitus Gene biology epigenetics business.industry Sequence Analysis RNA traumatic brain injury Methylation Original Articles DNA Methylation Fold change Differentially methylated regions Military Personnel Immunology DNA methylation biology.protein Cytokines Neurology (clinical) Inflammation Mediators 0305 other medical science business 030217 neurology & neurosurgery Biomarkers |
| Zdroj: | Journal of Neurotrauma |
| ISSN: | 1557-9042 0897-7151 |
| Popis: | Injuries from exposure to explosions rose dramatically during the Iraq and Afghanistan wars, which motivated investigations of blast-related neurotrauma and operational breaching. In this study, military “breachers” were exposed to controlled, low-level blast during a 10-day explosive breaching course. Using an omics approach, we assessed epigenetic, transcriptional, and inflammatory profile changes in blood from operational breaching trainees, with varying levels of lifetime blast exposure, along with daily self-reported symptoms (with tinnitus, headaches, and sleep disturbances as the most frequently reported). Although acute exposure to blast did not confer epigenetic changes, specifically in DNA methylation, differentially methylated regions (DMRs) with coordinated gene expression changes associated with chronic lifetime cumulative blast exposures were identified. The accumulative effect of blast showed increased methylation of PAX8 antisense transcript with coordinated repression of gene expression, which has been associated with sleep disturbance. DNA methylation analyses conducted in conjunction with reported symptoms of tinnitus in the low vs. high blast incidents groups identified DMRS in KCNE1 and CYP2E1 genes. KCNE1 and CYP2E1 showed the expected inverse correlation between DNA methylation and gene expression, which have been previously implicated in noise related hearing loss. Although no significant transcriptional changes were observed in samples obtained at the onset of the training course relative to chronic cumulative blast, we identified a large number of transcriptional perturbations acutely pre- versus post-blast exposure. Acutely, 67 robustly differentially expressed genes (fold change ≥1.5), including UFC1 and YOD1, ubiquitin-related proteins were identified. Inflammatory analyses of cytokines and chemokines revealed dysregulation of MCP-1, GCSF, HGF, MCSF, and RANTES acutely following blast exposure. These data show the importance of an omics approach, revealing that transcriptional and inflammatory biomarkers capture acute low-level blast overpressure exposure, whereas DNA methylation marks encapsulate chronic long-term symptoms. |
| Databáze: | OpenAIRE |
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