Gene and Stress History Interplay in Emergence of PTSD-like Features
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 C57BL/6j, DBA/2j and BALB/cj 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, DBA/2j developed a different strategy to evade Agg mice, which potentially contributed to its phenotypic resilience to Agg-E stress. Although Agg mice inflicted C57BL/6j and BALB/cj with equivalent numbers of strikes, BALB/cj displayed a distinct behavioral phenotype with delayed exhibition of a number of PTSD-like features. By contrast, C57BL/6j 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 C57BL/6j and BALB/cj 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 27, 2015
- Accession Number
- ADA621190
Entities
People
- Aarti Gautam
- James L. Meyerhoff
- Marti Jett
- Meskerem Jibitu
- Nabrun Chakraborty
- Rasha Hammamieh
- Seid Muhie
- Thereza C. De Lima
Organizations
- U.S. Army Center for Environmental Health Research