Blast induced neurotrauma leads to changes in the epigenome

Zachary S. Bailey, Venkata Siva Sai Sujith Sajja, W. Brad Hubbard, Pamela J. VandeVord

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

3 Scopus citations

Abstract

Blast induced neurotrauma (BINT) leads to widespread aberrant gene expression and molecular changes resulting in cognitive impairment. Enzymes such as HDAC2, HDAC6, SIRT1, DNMT1, DNMT3a and DNMT3b control histone acetylation and DNA methylation which play a major role in regulation of the transcriptome. Changes in the expression of these enzymes have been implicated in the pathology of traumatic brain injury (TBI) and Alzheimer's disease (AD). We hypothesize that blast exposure 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 time polymerase chain reaction and Western blot analyses were used to assess gene expression and protein level changes compared to sham. No significant changes were seen 24 hours after blast exposure. However, several changes were observed at 72 hours following blast exposure. There was a significant increase in expression of HDAC2 and HDAC6 in the hippocampus which correlated 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 exposure causes acute changes in gene expression and protein levels of epigenetic markers which correlate with changes observed in AD pathology. These epigenomic changes could provide novel targets for therapeutic interventions following BINT.

Original languageEnglish
Title of host publication52nd Annual Rocky Mountain Bioengineering Symposium and 52nd International ISA Biomedical Sciences Instrumentation Symposium 2015
Pages427-434
Number of pages8
ISBN (Electronic)9781510801981
StatePublished - 2015
Event52nd Annual Rocky Mountain Bioengineering Symposium and 52nd International ISA Biomedical Sciences Instrumentation Symposium 2015 - Salt Lake City, United States
Duration: Apr 10 2015Apr 12 2015

Publication series

Name52nd Annual Rocky Mountain Bioengineering Symposium and 52nd International ISA Biomedical Sciences Instrumentation Symposium 2015

Conference

Conference52nd Annual Rocky Mountain Bioengineering Symposium and 52nd International ISA Biomedical Sciences Instrumentation Symposium 2015
Country/TerritoryUnited States
CitySalt Lake City
Period4/10/154/12/15

Keywords

  • Blast neurotrauma
  • DNA methylation
  • Epigenetics
  • Histone acetylation

ASJC Scopus subject areas

  • Instrumentation
  • Bioengineering
  • Biotechnology
  • Biomedical Engineering

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