期刊
JOURNAL OF NEUROSCIENCE
卷 32, 期 20, 页码 6906-6916出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4012-11.2012
关键词
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资金
- European Research Council [260463]
- Israel Science Foundation
- Institute for the Study of Affective Neuroscience
- Legacy Heritage Biomedical Science Partnership
- Nella and Leon Benoziyo Center for Neurosciences
- European Research Council (ERC) [260463] Funding Source: European Research Council (ERC)
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.
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