Distinctive hippocampal and amygdalar cytoarchitectural changes underlie specific patterns of behavioral disruption following stress exposure in an animal model of PTSD
Distinctive hippocampal and amygdalar cytoarchitectural changes underlie specific patterns of behavioral disruption following stress exposure in an animal model of PTSD
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DOI：
10.1016/j.euroneuro.2014.09.009
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发表时间：
2014-12-01
影响因子：
5.6
通讯作者：
Kaplan, Zeev
中科院分区：
文献类型：
--
作者：
Cohen, Hagit;Kozlovsky, Nitsan;Kaplan, Zeev
在对压力的适应性和适应不良反应中已经观察到细胞结构和分子信号的改变，并且可能是所观察到的生理和行为变化的基础。在创伤后应激障碍动物模型中研究了应激暴露的行为反应与海马和杏仁核亚区域细胞结构变化之间的关系。在暴露于捕食者气味应激7天后，评估大鼠在高架十字迷宫和声学惊吓反应测试中的行为。24小时后收获脑。从CA 1，CA 3，齿状回亚区和基底外侧杏仁核的神经元进行重建，并进行Sholl分析和棘密度估计。在海马中评价糖皮质激素受体、脑源性神经营养因子、磷酸-NR 1-Ser-889、磷酸-GluR 1-Ser-845、磷酸-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-CREB-Ser-133。通过将个体大鼠回顾性分类为三个行为反应组来分析数据。海马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（PTSD样）行为中断与海马区广泛的神经元收缩和杏仁核的增殖有关。在最小行为反应者中，两种结构都没有显示出这种变化。部分行为反应仅与海马体的相同变化相关。必需的分子信号基因和内表型标记物的变化模式对应于结构和行为反应。海马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。(C)2014 Elsevier B.V.和ECNP。All rights reserved.
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 24 h 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. (C) 2014 Elsevier B.V. and ECNP. All rights reserved.