A Moderate Blast Exposure Results in Dysregulated Gene Network Activity Related to Cell Death, Survival, Structure, and Metabolism
Blast exposure is common in military personnel during training and combat operations, yet biological mechanisms related to cell survival and function that coordinate recovery remain poorly understood. This study explored how moderate blast exposure influences gene expression; specifically, gene-netw...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fneur.2020.00091/full |
| _version_ | 1818176209793581056 |
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| author | Katie A. Edwards Katie A. Edwards Vida Motamedi Nicole D. Osier Nicole D. Osier Hyung-Suk Kim Sijung Yun Young-Eun Cho Chen Lai Kristine C. Dell Walter Carr Peter Walker Stephen Ahlers Matthew LoPresti Angela Yarnell Anna Tschiffley Jessica M. Gill Jessica M. Gill |
| author_facet | Katie A. Edwards Katie A. Edwards Vida Motamedi Nicole D. Osier Nicole D. Osier Hyung-Suk Kim Sijung Yun Young-Eun Cho Chen Lai Kristine C. Dell Walter Carr Peter Walker Stephen Ahlers Matthew LoPresti Angela Yarnell Anna Tschiffley Jessica M. Gill Jessica M. Gill |
| author_sort | Katie A. Edwards |
| collection | DOAJ |
| description | Blast exposure is common in military personnel during training and combat operations, yet biological mechanisms related to cell survival and function that coordinate recovery remain poorly understood. This study explored how moderate blast exposure influences gene expression; specifically, gene-network changes following moderate blast exposure. On day 1 (baseline) of a 10-day military training program, blood samples were drawn, and health and demographic information collected. Helmets equipped with bilateral sensors worn throughout training measured overpressure in pounds per square inch (psi). On day 7, some participants experienced moderate blast exposure (peak pressure ≥5 psi). On day 10, 3 days post-exposure, blood was collected and compared to baseline with RNA-sequencing to establish gene expression changes. Based on dysregulation data from RNA-sequencing, followed by top gene networks identified with Ingenuity Pathway Analysis, a subset of genes was validated (NanoString). Five gene networks were dysregulated; specifically, two highly significant networks: (1) Cell Death and Survival (score: 42), including 70 genes, with 50 downregulated and (2) Cell Structure, Function, and Metabolism (score: 41), including 69 genes, with 41 downregulated. Genes related to ubiquitination, including neuronal development and repair: UPF1, RNA Helicase and ATPase (UPF1) was upregulated while UPF3 Regulator of Nonsense Transcripts Homolog B (UPF3B) was downregulated. Genes related to inflammation were upregulated, including AKT serine/threonine kinase 1 (AKT1), a gene coordinating cellular recovery following TBIs. Moderate blast exposure induced significant gene expression changes including gene networks involved in (1) cell death and survival and (2) cellular development and function. The present findings may have implications for understanding blast exposure pathology and subsequent recovery efforts. |
| first_indexed | 2024-12-11T20:12:33Z |
| format | Article |
| id | doaj.art-48f75e1c494540d8a19524cfe7232ba5 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-11T20:12:33Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-48f75e1c494540d8a19524cfe7232ba52022-12-22T00:52:16ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-02-011110.3389/fneur.2020.00091450135A Moderate Blast Exposure Results in Dysregulated Gene Network Activity Related to Cell Death, Survival, Structure, and MetabolismKatie A. Edwards0Katie A. Edwards1Vida Motamedi2Nicole D. Osier3Nicole D. Osier4Hyung-Suk Kim5Sijung Yun6Young-Eun Cho7Chen Lai8Kristine C. Dell9Walter Carr10Peter Walker11Stephen Ahlers12Matthew LoPresti13Angela Yarnell14Anna Tschiffley15Jessica M. Gill16Jessica M. Gill17National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, United StatesThe Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United StatesWake Forest School of Medicine, Wake Forest University, Winston-Salem, NC, United StatesSchool of Nursing, University of Texas at Austin, Austin, TX, United StatesDepartment of Neurology, University of Texas, Austin, TX, United StatesNational Institute of Nursing Research, National Institutes of Health, Bethesda, MD, United StatesNational Institute of Nursing Research, National Institutes of Health, Bethesda, MD, United StatesCollege of Nursing, University of Iowa, Iowa City, IA, United StatesNational Institute of Nursing Research, National Institutes of Health, Bethesda, MD, United StatesWalter Reed Army Institute of Research, Silver Spring, MD, United StatesWalter Reed Army Institute of Research, Silver Spring, MD, United StatesNaval Medical Research Center, Silver Spring, MD, United StatesNaval Medical Research Center, Silver Spring, MD, United StatesWalter Reed Army Institute of Research, Silver Spring, MD, United StatesWalter Reed Army Institute of Research, Silver Spring, MD, United StatesNaval Medical Research Center, Silver Spring, MD, United StatesNational Institute of Nursing Research, National Institutes of Health, Bethesda, MD, United StatesCNRM Co-Director Biomarkers Core, Uniformed Services University of the Health Sciences, Bethesda, MD, United StatesBlast exposure is common in military personnel during training and combat operations, yet biological mechanisms related to cell survival and function that coordinate recovery remain poorly understood. This study explored how moderate blast exposure influences gene expression; specifically, gene-network changes following moderate blast exposure. On day 1 (baseline) of a 10-day military training program, blood samples were drawn, and health and demographic information collected. Helmets equipped with bilateral sensors worn throughout training measured overpressure in pounds per square inch (psi). On day 7, some participants experienced moderate blast exposure (peak pressure ≥5 psi). On day 10, 3 days post-exposure, blood was collected and compared to baseline with RNA-sequencing to establish gene expression changes. Based on dysregulation data from RNA-sequencing, followed by top gene networks identified with Ingenuity Pathway Analysis, a subset of genes was validated (NanoString). Five gene networks were dysregulated; specifically, two highly significant networks: (1) Cell Death and Survival (score: 42), including 70 genes, with 50 downregulated and (2) Cell Structure, Function, and Metabolism (score: 41), including 69 genes, with 41 downregulated. Genes related to ubiquitination, including neuronal development and repair: UPF1, RNA Helicase and ATPase (UPF1) was upregulated while UPF3 Regulator of Nonsense Transcripts Homolog B (UPF3B) was downregulated. Genes related to inflammation were upregulated, including AKT serine/threonine kinase 1 (AKT1), a gene coordinating cellular recovery following TBIs. Moderate blast exposure induced significant gene expression changes including gene networks involved in (1) cell death and survival and (2) cellular development and function. The present findings may have implications for understanding blast exposure pathology and subsequent recovery efforts.https://www.frontiersin.org/article/10.3389/fneur.2020.00091/fullblastoverpressuregene expressionRNA-sequencingNanoString |
| spellingShingle | Katie A. Edwards Katie A. Edwards Vida Motamedi Nicole D. Osier Nicole D. Osier Hyung-Suk Kim Sijung Yun Young-Eun Cho Chen Lai Kristine C. Dell Walter Carr Peter Walker Stephen Ahlers Matthew LoPresti Angela Yarnell Anna Tschiffley Jessica M. Gill Jessica M. Gill A Moderate Blast Exposure Results in Dysregulated Gene Network Activity Related to Cell Death, Survival, Structure, and Metabolism Frontiers in Neurology blast overpressure gene expression RNA-sequencing NanoString |
| title | A Moderate Blast Exposure Results in Dysregulated Gene Network Activity Related to Cell Death, Survival, Structure, and Metabolism |
| title_full | A Moderate Blast Exposure Results in Dysregulated Gene Network Activity Related to Cell Death, Survival, Structure, and Metabolism |
| title_fullStr | A Moderate Blast Exposure Results in Dysregulated Gene Network Activity Related to Cell Death, Survival, Structure, and Metabolism |
| title_full_unstemmed | A Moderate Blast Exposure Results in Dysregulated Gene Network Activity Related to Cell Death, Survival, Structure, and Metabolism |
| title_short | A Moderate Blast Exposure Results in Dysregulated Gene Network Activity Related to Cell Death, Survival, Structure, and Metabolism |
| title_sort | moderate blast exposure results in dysregulated gene network activity related to cell death survival structure and metabolism |
| topic | blast overpressure gene expression RNA-sequencing NanoString |
| url | https://www.frontiersin.org/article/10.3389/fneur.2020.00091/full |
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