Ministry of Health, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Ministry of Health, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Eur Neuropsychopharmacol. 2014 Dec;24(12):1925-44. doi: 10.1016/j.euroneuro.2014.09.009. Epub 2014 Oct 14.
Alterations in cytoarchitecture and molecular signaling have been observed in adaptive and maladaptive responses to stress and presumably underlie the physiological and behavioral changes observed. The relationship between behavioral responses to stress exposure and changes in cytoarchitecture of subregions of the hippocampus and amygdala was investigated in an animal model of PTSD. Behaviors in elevated plus-maze and acoustic startle response tests were assessed in rats 7 days after exposure to predator scent stress. Brains were harvested 24h later. Neurons from CA1, CA3, and dentate gyrus subregions and basolateral amygdala were reconstructed and subjected to Sholl analysis and spine density estimation. Glucocorticoid receptor, brain-derived neurotrophic factor, phospho-NR1-Ser-889, phospho-GluR1-Ser-845, phospho-calcium/calmodulin dependent protein kinase II-Thy-286, post-synaptic density protein 95 and phospho-CREB-Ser-133 were evaluated in the hippocampus. Data were analyzed by retrospective classification of individual rats into three behavioral response groups. The extent and distribution of changes in the morphology of hippocampal and amygdalar dendrites was significantly associated with stress-induced behavioral response classification. Extreme (PTSD-like) behavioral disruption was associated with extensive neuronal retraction in the hippocampus and proliferation in the amygdala. Neither structure displayed such changes in minimal behavioral responders. Partial behavioral response was associated with identical changes in the hippocampus only. Patterns of change in requisite molecular signaling genes and endophenotypic markers corresponded to the structural and behavioral responses. The extent and distribution of changes in the cytoarchitecture of hippocampal and amygdalar subregions is directly related to the pattern of behavioral response of the individual to stress exposure.
适应性和失调性应激反应中观察到细胞结构和分子信号的改变，推测这些改变是观察到的生理和行为变化的基础。在创伤后应激障碍的动物模型中，研究了应激暴露后行为反应与海马体和杏仁核亚区细胞结构变化之间的关系。在暴露于捕食者气味应激后 7 天，通过高架十字迷宫和听觉惊跳反应测试评估大鼠的行为。24 小时后收获大脑。重建 CA1、CA3 和齿状回亚区以及基底外侧杏仁核的神经元，并进行 Sholl 分析和棘密度估计。评估海马体中的糖皮质激素受体、脑源性神经营养因子、磷酸化-NR1-Ser-889、磷酸化-GluR1-Ser-845、磷酸化钙/钙调蛋白依赖性蛋白激酶 II-Thy-286、突触后密度蛋白 95 和磷酸化-CREB-Ser-133。通过将个体大鼠分为三个行为反应组进行回顾性分类来分析数据。海马体和杏仁核树突形态变化的程度和分布与应激诱导的行为反应分类显著相关。极端（类似 PTSD）行为障碍与海马体神经元回缩和杏仁核增殖有关。在最小行为反应者中，两种结构均未显示出这种变化。部分行为反应仅与海马体的相同变化相关。必需分子信号基因和表型标记的变化模式与结构和行为反应相对应。海马体和杏仁核亚区细胞结构变化的程度和分布与个体对应激暴露的行为反应模式直接相关。
