Szklarczyk K, Korostynski M, Golda S, Solecki W, Przewlocki R
Department of Molecular Neuropharmacology, Institute of Pharmacology PAS, Krakow, Poland.
Genes Brain Behav. 2012 Nov;11(8):977-85. doi: 10.1111/j.1601-183X.2012.00850.x.
Post-traumatic stress disorder (PTSD) is an anxiety disorder that develops in predisposed individuals following a terrifying event. Studies on isogenic animal populations might explain susceptibility to PTSD by revealing associations between the molecular and behavioural consequences of traumatic stress. Our study employed four inbred mouse strains to search for differences in post-stress response to a 1.5-mA electric foot shock. One day to 6 weeks after the foot shock anxiety, depression and addiction-like phenotypes were assessed. In addition, expression levels of selected stress-related genes were analysed in hippocampus and amygdala. C57BL/6J mice exhibited up-regulation in the expression of Tsc22d3, Nfkbia, Plat and Crhr1 genes in both brain regions. These alterations were associated with an increase of sensitized fear and depressive-like behaviour over time. Traumatic stress induced expression of Tsc22d3, Nfkbia, Plat and Fkbp5 genes and developed social withdrawal in DBA/2J mice. In 129P3/J strain, exposure to stress produced the up-regulation of Tsc22d3 and Nfkbia genes and enhanced sensitivity to the rewarding properties of morphine. Whereas, SWR/J mice displayed increase only in Pdyn expression in the amygdala and had the lowest conditioned fear. Our results reveal a complex genetic background of phenotypic variation in response to stress and indicate the SWR/J strain as a valuable model of stress resistance. We found potential links between the alterations in expression of Tsc22d3, Nfkbia and Pdyn, and different aspects of susceptibility to stress.
创伤后应激障碍（PTSD）是一种焦虑症，在经历可怕事件后，易感个体中会出现这种病症。对同基因动物群体的研究可能通过揭示创伤应激的分子和行为后果之间的关联来解释对PTSD的易感性。我们的研究使用了四种近交系小鼠品系，以寻找对1.5毫安电足击的应激后反应差异。在足部电击后1天至6周，评估焦虑、抑郁和成瘾样表型。此外，分析了海马体和杏仁核中选定的应激相关基因的表达水平。C57BL/6J小鼠在两个脑区的Tsc22d3、Nfkbia、Plat和Crhr1基因表达均上调。随着时间的推移，这些改变与致敏恐惧和抑郁样行为的增加有关。创伤应激诱导DBA/2J小鼠中Tsc22d3、Nfkbia、Plat和Fkbp5基因的表达，并导致社交退缩。在129P3/J品系中，应激暴露使Tsc22d3和Nfkbia基因上调，并增强了对吗啡奖赏特性的敏感性。而SWR/J小鼠仅在杏仁核中Pdyn表达增加，且条件性恐惧最低。我们的结果揭示了应激反应表型变异的复杂遗传背景，并表明SWR/J品系是一种有价值的应激抗性模型。我们发现Tsc22d3、Nfkbia和Pdyn表达的改变与应激易感性的不同方面之间存在潜在联系。
