Post-traumatic stress behavioural responses in inbred mouse strains: can genetic predisposition explain phenotypic vulnerability?
Post-traumatic stress behavioural responses in inbred mouse strains: can genetic predisposition explain phenotypic vulnerability?
复制标题
DOI：
10.1017/s1461145707007912
复制
发表时间：
2008-05-01
影响因子：
4.8
通讯作者：
Kaplan, Zeev
中科院分区：
文献类型：
--
作者：
Cohen, Hagit;Geva, Amir B.;Kaplan, Zeev
对双胞胎和创伤后应激障碍（PTSD）患者家庭的临床研究提出了关于PTSD可能遗传易感性的问题。使用暴露于应激范式的同基因动物群体的研究可以阐明基因型和环境对内表型表达的相对贡献。显示严重受损的行为反应捕食者气味压力（PSS）的个人的患病率进行了评估，在6个近交系的小鼠在PTSD的动物模型，根据他们的行为反应的程度将个人分组。品系的选择是基于这些小鼠在转基因研究中的频繁使用。极端行为反应的患病率在高架十字迷宫和声学惊吓反应范例，顺序进行，进行了评估，在基线和7天后，PSS曝光之间和内部菌株，并比较循环皮质酮水平的差异。狭义性状遗传力通过比较株间方差与总方差来确定。虽然证明了焦虑样行为的菌株特异性差异，但结果显示每个近交系内的反应模式存在显著程度的个体变异性，焦虑样行为的基线遗传因子为30%，但对压力暴露的反应仅为10%。发现基线焦虑样行为不能预测暴露后的行为反应。个体对压力的反应是多因素的，环境因素在表征个体对压力暴露的反应方面起着主导作用，尽管有重要的遗传基础。
Clinical studies of twin pairs and families of post-traumatic stress disorder (PTSD) patients raise questions as to possible genetic predisposition to PTSD. Studies using isogenic animal populations exposed to a stress paradigm could elucidate the relative contributions of genotype and environment to endophenotypic expression. The prevalence of individuals displaying severely compromised behavioural responses to predator scent stress (PSS) was assessed in six inbred strains of mice in an animal model of PTSD that classifies individuals into groups according to the degree of their behavioural response. The choice of strains was based on the frequent use of these mice in transgenic research. The prevalence of extreme behavioural response in the elevated plus maze and the acoustic startle response paradigms, performed in sequence, was assessed at baseline and 7 d after PSS exposure between and within strains, and compared to differences in circulating corticosterone levels. Narrow-sense trait heritability was determined by comparing the between-strain variance to the total variance. Although strain-specific differences in anxiety-like behaviours were demonstrated, the results revealed a significant degree of individual variability in response patterns within each of the inbred strains, yielding a baseline heritability factor for anxiety-like behaviours of 30%, but only 10% for response to stress exposure. Baseline anxiety-like behaviours were found not to be predictive of post-exposure behavioural responses. The response of the individual to stress is multifactorial and environmental factors play a predominant role in characterizing the individual response to stress exposure, although there are significant genetic underpinnings.