BLAST INDUCED NEUROTRAUMA LEADS TO CHANGES IN THE EPIGENOME

摘要

Blast induced neurotrauma (BINT) leads to widespread aberrant gene expression and molecular changes resulting in cognitiveimpairment. Enzymes such as HDAC2, HDAC6, SIRT1, DNMT1, DNMT3a and DNMT3b control histone acetylation andDNA methylation which play a major role in regulation of the transcriptome. Changes in the expression of these enzymes havebeen implicated in the pathology of traumatic brain injury (TBI) and Alzheimer’s disease (AD). We hypothesize that blastexposure will lead to changes in the expression of these enzymes which play a key role in injury progression and pathology.This study looked to identify epigenome changes in the acute stages of BINT using an established rodent model. Real timepolymerase chain reaction and Western blot analyses were used to assess gene expression and protein level changes comparedto sham. No significant changes were seen 24 hours after blast exposure. However, several changes were observed at 72 hoursfollowing blast exposure. There was a significant increase in expression of HDAC2 and HDAC6 in the hippocampus whichcorrelated with elevated HDAC2 protein levels. SIRT1, DNMT3a and DNMT3b levels were all reduced in the hippocampus.In the medial prefrontal cortex, DNMT1 and DNMT3b were significantly reduced. The results indicated that blast exposurecauses acute changes in gene expression and protein levels of epigenetic markers which correlate with changes observed in ADpathology. These epigenomic changes could provide novel targets for therapeutic interventions following BINT.