Chronic Stress-induced Behaviors Correlate with Exacerbated Acute Stress-induced Cingulate Cortex and Ventral Hippocampus Activation
Chronic Stress-induced Behaviors Correlate with Exacerbated Acute Stress-induced Cingulate Cortex and Ventral Hippocampus Activation
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DOI：
10.1016/j.neuroscience.2020.05.034
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发表时间：
2020-08-01
期刊：
影响因子：
3.3
通讯作者：
Sibille, Etienne
中科院分区：
文献类型：
--
作者：
Fee, Corey;Prevot, Thomas;Sibille, Etienne
皮质边缘脑区的活动改变是与压力有关的疾病的标志，包括情绪障碍、神经退行性疾病和物质滥用障碍。急性应激适应性地招募大脑区域特定的功能来应对，而慢性应激下的持续激活可能会压倒反馈机制，并导致病理性细胞和行为反应。神经机制失调的压力反应，以及它们如何有助于行为缺陷的特点很差。在这里，我们测试了小鼠先前暴露于慢性束缚应激（CRS）或不可预测的慢性轻度应激（UCMS）是否会改变对急性应激的功能反应，以及这些变化是否与慢性应激诱导的行为缺陷有关。更具体地说，我们评估了24个应激和情绪相关脑区中由c-Fos+细胞计数索引的急性应激诱导的功能激活，并确定功能激活的变化是否与慢性应激诱导的行为障碍有关，通过主成分分析（PCA）进行跨维度总结。结果表明，CRS和UCMS导致会聚生理和焦虑样缺陷，而工作和短期记忆仅在UCMS小鼠中受损。CRS和UCMS暴露加剧了前扣带皮层（ACC）24 b区和腹侧海马（vHPC）CA 1，CA 3和下托的急性应激功能激活。在失调的大脑区域，功能激活水平与主成分呈正相关，反映了与压力相关疾病相关的行为缺陷的差异。我们的数据支持一个失调的压力反应，改变功能皮质边缘兴奋/抑制平衡，和适应不良行为的表达之间的关联。(C)2020年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Altered activity of corticolimbic brain regions is a hallmark of stress-related illnesses, including mood disorders, neurodegenerative diseases, and substance abuse disorders. Acute stress adaptively recruits brain region-specific functions for coping, while sustained activation under chronic stress may overwhelm feedback mechanisms and lead to pathological cellular and behavioral responses. The neural mechanisms underlying dysregulated stress responses and how they contribute to behavioral deficits are poorly characterized. Here, we tested whether prior exposure to chronic restraint stress (CRS) or unpredictable chronic mild stress (UCMS) in mice could alter functional response to acute stress and whether these changes are associated with chronic stress-induced behavioral deficits. More specifically, we assessed acute stress-induced functional activation indexed by c-Fos+ cell counts in 24 stress- and mood-related brain regions, and determined if changes in functional activation were linked to chronic stress-induced behavioral impairments, summarized across dimensions through principal component analysis (PCA). Results indicated that CRS and UCMS led to convergent physiological and anxiety-like deficits, whereas working and short-term memory were impaired only in UCMS mice. CRS and UCMS exposure exacerbated functional activation by acute stress in anterior cingulate cortex (ACC) area 24b and ventral hippocampal (vHPC) CA1, CA3, and subiculum. In dysregulated brain regions, levels of functional activation were positively correlated with principal components reflecting variance across behavioral deficits relevant to stress-related disorders. Our data supports an association between a dysregulated stress response, altered functional corticolimbic excitation/inhibition balance, and the expression of maladaptive behaviors. (C) 2020 IBRO. Published by Elsevier Ltd. All rights reserved.