Moderate blast exposure alters gene expression and levels of amyloid precursor protein

被引:37
作者
Gill, Jessica [1 ]
Cashion, Ann [2 ]
Osier, Nicole [2 ]
Arcurio, Lindsay [2 ]
Motamedi, Vida [2 ]
Dell, Kristine C. [3 ]
Carr, Walter [4 ]
Kim, Hyung-Suk [2 ]
Yun, Sijung [2 ]
Walker, Peter [5 ]
Ahlers, Stephen [5 ]
LoPresti, Matthew [3 ]
Yarnell, Angela [3 ]
机构
[1] Uniformed Serv Univ Hlth Sci, Intramural Res Program, CNRM Co Director Biomarkers Core, Bethesda, MD 20814 USA
[2] NINR, NIH, Bethesda, MD 20892 USA
[3] Walter Reed Army Inst Res, Silver Spring, MD USA
[4] Army Med Res & Mat Command, Ft Detrick, MD USA
[5] Naval Med Res Ctr, Silver Spring, MD USA
基金
美国国家卫生研究院;
关键词
TRAUMATIC BRAIN-INJURY; AXONAL INJURY; ALZHEIMERS-DISEASE; MESSENGER-RNA; NEUROPROTECTION; MARKER; MODEL;
D O I
10.1212/NXG.0000000000000186
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Objective: To explore gene expression after moderate blast exposure (vs baseline) and proteomic changes after moderate- (vs low-) blast exposure.& para;& para;Methods: Military personnel (N = 69) donated blood for quantification of protein level, and peak pressure exposures were detected by helmet sensors before and during a blast training program (10 days total). On day 7, some participants (n = 29) sustained a moderate blast (mean peak pressure = 7.9 psi) and were matched to participants with no/low-blast exposure during the training (n = 40). PAXgene tubes were collected from one training site at baseline and day 10; RNA-sequencing day 10 expression was compared with each participant's own baseline samples to identify genes and pathways differentially expressed in moderate blast-exposed participants. Changes in amyloid precursor protein (APP) from baseline to the day of blast and following 2 days were evaluated. Symptoms were assessed using a self-reported form.& para;& para;Results: We identified 1,803 differentially expressed genes after moderate blast exposure; the most altered network was APP. Significantly reduced levels of peripheral APP were detected the day after the moderate blast exposure and the following day. Protein concentrations correlated with the magnitude of the moderate blast exposure on days 8 and 9. APP concentrations returned to baseline levels 3 days following the blast, likely due to increases in the genetic expression of APP. Onset of concentration problems and headaches occurred after moderate blast.& para;& para;Conclusions: Moderate blast exposure results in a signature biological profile that includes acute APP reductions, followed by genetic expression increases and normalization of APP levels; these changes likely influence neuronal recovery.
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页数:9
相关论文
共 26 条
[1]   Ceruloplasmin and β-amyloid precursor protein confer neuroprotection in traumatic brain injury and lower neuronal iron [J].
Ayton, Scott ;
Zhang, Moses ;
Roberts, Blaine R. ;
Lam, Linh Q. ;
Lind, Monica ;
McLean, Catriona ;
Bush, Ashley I. ;
Frugier, Tony ;
Crack, Peter J. ;
Duce, James A. .
FREE RADICAL BIOLOGY AND MEDICINE, 2014, 69 :331-337
[2]   STAINING OF AMYLOID PRECURSOR PROTEIN TO STUDY AXONAL DAMAGE IN MILD HEAD-INJURY [J].
BLUMBERGS, PC ;
SCOTT, G ;
MANAVIS, J ;
WAINWRIGHT, H ;
SIMPSON, DA ;
MCLEAN, AJ .
LANCET, 1994, 344 (8929) :1055-1056
[3]   Ubiquitin carboxy-terminal hydrolase-L1 as a serum neurotrauma biomarker for exposure to occupational low-level blast [J].
Carr, Walter ;
Yarnell, Angela M. ;
Ong, Ricardo ;
Walilko, Timothy ;
Kamimori, Gary H. ;
da Silva, Uade ;
McCarron, Richard M. ;
LoPresti, Matthew L. .
FRONTIERS IN NEUROLOGY, 2015, 6
[4]   Subacute Changes in Cleavage Processing of Amyloid Precursor Protein and Tau following Penetrating Traumatic Brain Injury [J].
Cartagena, Casandra M. ;
Mountney, Andrea ;
Hwang, Hye ;
Swiercz, Adam ;
Rammelkamp, Zoe ;
Boutte, Angela M. ;
Shear, Deborah A. ;
Tortella, Frank C. ;
Schmid, Kara E. .
PLOS ONE, 2016, 11 (07)
[5]  
De Gasperi Rita, 2012, Front Neurol, V3, P177, DOI 10.3389/fneur.2012.00177
[6]   A novel closed-body model of spinal cord injury caused by high-pressure air blasts produces extensive axonal injury and motor impairments [J].
del Mar, Nobel ;
von Buttlar, Xinyu ;
Yu, Angela S. ;
Guley, Natalie H. ;
Reiner, Anton ;
Honig, Marcia G. .
EXPERIMENTAL NEUROLOGY, 2015, 271 :53-71
[7]   Influence of Combat Blast-Related Mild Traumatic Brain Injury Acute Symptoms on Mental Health and Service Discharge Outcomes [J].
Eskridge, Susan L. ;
Macera, Caroline A. ;
Galarneau, Michael R. ;
Holbrook, Troy L. ;
Woodruff, Susan I. ;
MacGregor, Andrew J. ;
Morton, Deborah J. ;
Shaffer, Richard A. .
JOURNAL OF NEUROTRAUMA, 2013, 30 (16) :1391-1397
[8]   BETA-AMYLOID PRECURSOR PROTEIN (BETA-APP) AS A MARKER FOR AXONAL INJURY AFTER HEAD-INJURY [J].
GENTLEMAN, SM ;
NASH, MJ ;
SWEETING, CJ ;
GRAHAM, DI ;
ROBERTS, GW .
NEUROSCIENCE LETTERS, 1993, 160 (02) :139-144
[9]   Military personnel with chronic symptoms following blast traumatic brain injury have differential expression of neuronal recovery and epidermal growth factor receptor genes [J].
Heinzelmann, Morgan ;
Reddy, Swarnalatha Y. ;
French, Louis M. ;
Wang, Dan ;
Lee, Hyunhwa ;
Barr, Taura ;
Baxter, Tristin ;
Mysliwiec, Vincent ;
Gill, Jessica .
FRONTIERS IN NEUROLOGY, 2014, 5
[10]   Enhanced production of amyloid precursor protein mRNA by peripheral mononuclear blood cell in Alzheimer's disease [J].
Jiang, SD ;
Zhang, MY ;
Ren, DM ;
Tang, GM ;
Lin, SC ;
Qian, YP ;
Zhang, Y ;
Jiang, KD ;
Li, F ;
Wang, DX .
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2003, 118B (01) :99-102