METHODS: We used a Lewis rat model that incorporates critical elements of chronic psychosocial stress, such as uncontrollability, unpredictability, lack of social support, and re-experiencing of trauma.
RESULTS: Chronic stress during adolescence reduced the acoustic startle reflex and social interactions while increasing extracellular free water content and TACE/ADAM17 mRNA levels in the medial prefrontal cortex. Chronic stress altered various ethological behavioral domains in the observation home cages (decreased ingestive behaviors and increased walking, grooming, and rearing behaviors). A group of rats was injected intracerebrally either with a novel Accell™ SMARTpool TACE/ADAM17 siRNA or a corresponding siRNA vehicle (control). The RNAscope Multiplex Fluorescent v2 Assay was used to visualize mRNA expression. Automated puncta quantification and analyses demonstrated that TACE/ADAM17 siRNA administration reduced TACE/ADAM17 mRNA levels in the medial prefrontal cortex (59% reduction relative to control). We found that the rats that received prefrontal cortical TACE/ADAM17 siRNA administration exhibited altered eating patterns (e.g., increased food intake and time in the feeding zone during the light cycle).
CONCLUSIONS: This study supports that the prefrontal cortex is sensitive to adolescent chronic stress and suggests that TACE/ADAM17 may be involved in the brain responses to stress.
方法:我们使用了Lewis大鼠模型,该模型包含了慢性社会心理压力的关键要素,比如不可控性,不可预测性,缺乏社会支持,重新体验创伤。
结果:青春期的慢性应激降低了听觉惊吓反射和社会相互作用,同时增加了内侧前额叶皮层的细胞外游离水含量和TACE/ADAM17mRNA水平。慢性压力改变了观察家庭笼子中的各种行为学行为域(减少的摄食行为和增加的行走,梳理,和饲养行为)。一组大鼠脑内注射新型Accell™SMARTpuneTACE/ADAM17siRNA或相应的siRNA载体(对照)。RNAscope多重荧光v2测定用于可视化mRNA表达。自动点定量和分析表明,TACE/ADAM17siRNA施用降低内侧前额叶皮质中的TACE/ADAM17mRNA水平(相对于对照降低59%)。我们发现接受前额叶皮质TACE/ADAM17siRNA给药的大鼠表现出改变的进食模式(例如,在光照周期内增加食物摄入量和喂养区的时间)。
结论:这项研究支持前额叶皮质对青少年慢性应激敏感,并提示TACE/ADAM17可能参与大脑对应激的反应。