TY - JOUR
T1 - A Moderate Blast Exposure Results in Dysregulated Gene Network Activity Related to Cell Death, Survival, Structure, and Metabolism
AU - Edwards, Katie A.
AU - Motamedi, Vida
AU - Osier, Nicole D.
AU - Kim, Hyung Suk
AU - Yun, Sijung
AU - Cho, Young Eun
AU - Lai, Chen
AU - Dell, Kristine C.
AU - Carr, Walter
AU - Walker, Peter
AU - Ahlers, Stephen
AU - LoPresti, Matthew
AU - Yarnell, Angela
AU - Tschiffley, Anna
AU - Gill, Jessica M.
N1 - Publisher Copyright:
© 2020, At least a portion of this work is authored by Katie A. Edwards, Vida Motamedi, Nicole D. Osier, Hyung-Suk Kim, Young-Eun Cho, Chen Lai, Kristine C. Dell, Walter Carr, Peter Walker, Stephen Ahlers, Matthew LoPresti, Angela Yarnell, Anna Tschiffley and Jessica M. Gill on behalf of the U.S. Government and, as regards Katie A. Edwards, Vida Motamedi, Nicole D. Osier, Hyung-Suk Kim, Young-Eun Cho, Chen Lai, Kristine C. Dell, Walter Carr, Peter Walker, Stephen Ahlers, Matthew LoPresti, Angela Yarnell, Anna Tschiffley and Jessica M. Gill and the U.S. Government, is not subject to copyright protection in the United States. Foreign and other copyrights may apply.
PY - 2020/2/26
Y1 - 2020/2/26
N2 - 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.
AB - 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.
KW - NanoString
KW - RNA-sequencing
KW - blast
KW - gene expression
KW - overpressure
UR - http://www.scopus.com/inward/record.url?scp=85082408823&partnerID=8YFLogxK
U2 - 10.3389/fneur.2020.00091
DO - 10.3389/fneur.2020.00091
M3 - Article
AN - SCOPUS:85082408823
SN - 1664-2295
VL - 11
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 91
ER -