Accession Number:

ADA621190

Title:

Gene and Stress History Interplay in Emergence of PTSD-like Features

Descriptive Note:

Journal article

Corporate Author:

ARMY CENTER FOR ENVIRONMENTAL HEALTH RESEARCH FORT DETRICK MD

Report Date:

2015-05-27

Pagination or Media Count:

14.0

Abstract:

Systematically distinguishing genetic liability from other contributing factors is critical for designing a preventive strategy for post-traumatic stress disorder PTSD. To address this issue, we investigated a murine model exposing C57BL6j, DBA2j and BALBcj mice to repeated stress via exposure to conspecific aggressors Agg-E. Na ve mice from each strain were subjected to the proximity of aggressor Agg mice for 6 h using a cage-within-a-cage paradigm, which was repeated for 5 or 10 days with intermittent and unpredictable direct contact with Agg mice. During the Agg-E stress, DBA2j developed a different strategy to evade Agg mice, which potentially contributed to its phenotypic resilience to Agg-E stress. Although Agg mice inflicted C57BL6j and BALBcj with equivalent numbers of strikes, BALBcj displayed a distinct behavioral phenotype with delayed exhibition of a number of PTSD-like features. By contrast, C57BL6j mice displayed unique vulnerability to Agg-E stress induced myocardopathy, possibly attributable to their particular susceptibility to hypoxia. A group of genes Bdnf, Ngf, Zwint, Cckbr, Slc6a4, Fkbp5 linked to PTSD and synaptic plasticity were significantly altered in C57BL6j and BALBcj Agg-E mice. Contributions of Agg-E stress history and genotypic heterogeneity emerged as the key mediators of PTSD-like features. Linking genetic components to specific phenotypic and pathological features could have potential clinical implications.

Subject Categories:

  • Psychology
  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research
  • Stress Physiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE