title: Susceptibility to PTSD-like behavior is mediated by corticotropin-releasing factor receptor type 2 levels in the bed nucleus of the stria terminalis.
abstract: Posttraumatic stress disorder (PTSD) is a debilitating disease, which affects 8-10% of the population exposed to traumatic events. The factors that make certain individuals susceptible to PTSD and others resilient are currently unknown. Corticotropin-releasing factor receptor type 2 (CRFR2) has been implicated in mediating stress coping mechanisms. Here, we use a physiological PTSD-like animal model and an in-depth battery of tests that reflect the symptomology of PTSD to separate mice into subpopulations of "PTSD-like" and "Resilient" phenotypes. PTSD-like mice are hypervigilant, hyperalert, insomniac, have impaired attention and risk assessment, as well as accompanying attenuated corticosterone levels. Intriguingly, PTSD-like mice show long-term robust upregulation of BNST-CRFR2 mRNA levels, and BNST-CRFR2-specific lentiviral knockdown reduces susceptibility to PTSD-like behavior. Additionally, using a BNST mRNA expression array, PTSD-like mice exhibit a general transcriptional attenuation profile, which was associated with upregulation of the BNST-deacetylation enzyme, HDAC5. We suggest PTSD to be a disease of maladaptive coping.
authors.affiliation: Departments of Neurobiology and  Veterinary Resources, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Lebow
authors.forename: Adi
authors.initials: A
authors.lastname: Neufeld-Cohen
authors.forename: Yael
authors.initials: Y
authors.lastname: Kuperman
authors.forename: Michael
authors.initials: M
authors.lastname: Tsoory
authors.forename: Shosh
authors.initials: S
authors.lastname: Gil
authors.forename: Alon
authors.initials: A
authors.lastname: Chen
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques / Q000379:methods / Q000523:psychology; D006655:Histone Deacetylases / Q000378:metabolism; D051379:Mice; D018019:Receptors, Corticotropin-Releasing Hormone / Q000096:biosynthesis* / Q000235:genetics; D055500:Resilience, Psychological; D012686:Septal Nuclei / Q000378:metabolism*; D013313:Stress Disorders, Post-Traumatic / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D015854:Up-Regulation
chemical_list: C101518:CRF(2alpha) receptor; D018019:Receptors, Corticotropin-Releasing Hormone; C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases; D003345:Corticosterone