title: 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). Naïve 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.
authors.affiliation: US Army Center for Environmental Health Research, Fort Detrick, MD 21702-5010, USA.
authors.forename: Nabarun
authors.initials: N
authors.lastname: Chakraborty
authors.affiliation: US Army Center for Environmental Health Research, Fort Detrick, MD 21702-5010, USA.
authors.forename: James
authors.initials: J
authors.lastname: Meyerhoff
authors.affiliation: US Army Center for Environmental Health Research, Fort Detrick, MD 21702-5010, USA.
authors.forename: Aarti
authors.initials: A
authors.lastname: Gautam
authors.affiliation: US Army Center for Environmental Health Research, Fort Detrick, MD 21702-5010, USA.
authors.forename: Seid
authors.initials: S
authors.lastname: Muhie
authors.affiliation: US Army Center for Environmental Health Research, Fort Detrick, MD 21702-5010, USA.
authors.forename: Meskerem
authors.initials: M
authors.lastname: Jibitu
authors.affiliation: Federal University of Santa Catarina - Department of Pharmacology, Florianopolis, SC, Brazil.
authors.forename: Thereza C M
authors.initials: TC
authors.lastname: De Lima
authors.affiliation: US Army Center for Environmental Health Research, Fort Detrick, MD 21702-5010, USA. Electronic address: Rasha.Hammamieh1.civ@mail.mil.
authors.forename: Rasha
authors.initials: R
authors.lastname: Hammamieh
authors.affiliation: US Army Center for Environmental Health Research, Fort Detrick, MD 21702-5010, USA.
authors.forename: Marti
authors.initials: M
authors.lastname: Jett
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology; D051379:Mice; D009473:Neuronal Plasticity / Q000235:genetics*; D010641:Phenotype; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics* / Q000503:physiopathology
keywords: Aggressor exposed model; Gene–environment model; Mouse behavior; Mouse strain differences; Post-traumatic stress disorder (PTSD)