Genome-wide analysis of stress-exposure-associated and exposure-related individual differences associated amygdala gene expression in males and females.

Delineating the molecular basis of individual differences in the stress response is critical to understanding the pathophysiology and treatment of posttraumatic stress disorder (PTSD). In this study, 7 d after predator-scent-stress (PSS) exposure, male and female rats were classified into vulnerable (i.e., “PTSD-like”) and resilient (i.e.,minimally affected) phenotypes on the basis of their performance on a variety of behavioral measures. Genome-wide expression profiling in blood and two limbic brain regions (amygdala and hippocampus), followed by quantitative PCR validation, was performed in these two groups of animals, as well as in an unexposed control group. Differentially expressed genes were identified in blood and brain associated with PSS-exposure and with distinct behavioral profiles postexposure. There was a small but significant between-tissue overlap (4–21%) for the genes associated with exposure-related individual differences, indicating convergent gene expression in both sexes. To uncover convergent signaling pathways across tissue and sex, upstream activated/deactivated transcription factorswere first predicted for each tissue and then the respective pathways were identified. Glucocorticoid receptor (GR) signaling was the only convergent pathway associatedwith individual differences when using the most stringent statistical threshold.阐明应激反应个体差异的分子机制，对于理解创伤后应激障碍（posttraumatic stress disorder, PTSD）的病理生理学及治疗方案至关重要。本研究中，研究人员在雄性与雌性大鼠暴露于捕食者气味应激（predator-scent-stress, PSS）7天后，基于多项行为学检测指标的表现，将其分为类PTSD的易感表型与受影响极小的抵抗表型。随后，研究人员针对这两组大鼠及未暴露的对照组大鼠，开展了血液与两处边缘脑区（limbic brain regions，杏仁核（amygdala）与海马体（hippocampus））的全基因组表达谱分析（genome-wide expression profiling），并通过定量PCR（quantitative PCR）完成验证。研究人员在血液与脑组织中鉴定出与PSS暴露及暴露后不同行为表型相关的差异表达基因（differentially expressed genes）。与暴露相关个体差异相关的基因在不同组织间存在4%至21%的小幅但显著的重叠，表明雌雄两性均存在趋同的基因表达模式。为揭示跨组织与性别的趋同信号通路，研究人员首先预测了各组织中上游激活/失活的转录因子（transcription factors），随后鉴定出对应的信号通路。在采用最严格的统计阈值时，糖皮质激素受体（Glucocorticoid receptor, GR）信号通路是唯一与个体差异相关的趋同通路。