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Publication : Gene and stress history interplay in emergence of PTSD-like features.

First Author  Chakraborty N Year  2015
Journal  Behav Brain Res Volume  292
Pages  266-77 PubMed ID  26025510
Mgi Jnum  J:227141 Mgi Id  MGI:5699790
Doi  10.1016/j.bbr.2015.05.038 Citation  Chakraborty N, et al. (2015) Gene and stress history interplay in emergence of PTSD-like features. Behav Brain Res 292:266-77
abstractText  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). Naive mice from each strain were subjected to the proximity of aggressor (Agg) mice for 6h 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.
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