DID YOU KNOW? DTIC has over 3.5 million final reports on DoD funded research, development, test, and evaluation activities available to our registered users. Click
HERE to register or log in.
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.
Distribution Statement:
APPROVED FOR PUBLIC RELEASE
