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

Objective: Blast induced traumatic brain injuries are a signature injury of recent war campaigns; yet little is known about the biological mechanisms underlying blast exposures. Methods: In a group of military personnel (N = 69), prior to, and on each day of a blast training program (10 days total), blood was collected; throughout training, blast exposure measures were detected by helmet sensors to determine the mean peak pressure in pounds per square inch (psi). 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). Results: RNA-seq identified 1,803 dysregulated genes, including 746 up-regulated genes and 1,058 down-regulated genes following a moderate blast exposure. The IPA showed the APP gene network to be most dysregulated following blast, with an IPA network score of 43. Real-time qPCR was used to validate the expression changes for four genes 4 genes, namely: amyloid precursor protein (APP), amyloid precursor-like protein 2 (APLP2), nicastrin (NCSTN) and NEDD8 Activating Enzyme E1 Subunit 1 (NAE1) and significant dysregulation of these genes was confirmed (p = 0.00083476, p = 0.000105, p = 0.000673 and p = 0.043145, respectively). 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. Overall design: miRNA profiling of 24 human blood samples at two time points to study PTSD