Duke University Medical Center, Department of Cell Biology, Durham, NC 27710, United States; Villanova University, Department of Psychological and Brain Sciences, Villanova, PA 19085, United States.
Duke University Medical Center, Department of Cell Biology, Durham, NC 27710, United States.
Neuroscience. 2018 Mar 1;373:122-136. doi: 10.1016/j.neuroscience.2018.01.018. Epub 2018 Jan 16.
The association between stress and mental illness has been well documented, but the molecular consequences of repeated exposure to stress have not been completely identified. The present study sought to elucidate the combinatorial effects of early-life maternal separation stress and adult social defeat stress on alterations in signal transduction and gene expression that have been previously implicated in susceptibility to psychosocial stress. Molecular analyses were performed in the prelimbic/infralimbic cortex, amygdala, and nucleus accumbens, three brain regions that have been suggested to play critical roles in determining stress responses. The current data reveal that both maternal separation and social defeat significantly impact the expression of genes involved in histone methylation and the β-catenin-, endogenous opioid-, neurotrophin-, and glucocorticoid signaling pathways. Although the effects of maternal separation and social defeat were largely non-overlapping, a subset of genes in each brain region were governed by additive, opposing, or other types of interactions between these stress paradigms, thus highlighting potential molecular mechanisms through which these stressors might coordinately regulate brain function and behavior.
压力与精神疾病之间的关联已有充分的文献记载，但反复暴露于压力下的分子后果尚未完全确定。本研究旨在阐明早期母婴分离应激和成年社交挫败应激对信号转导和基因表达的组合效应的阐明，这些信号转导和基因表达先前被认为与易患社会心理应激有关。分子分析在三个被认为在决定应激反应中起关键作用的脑区（前额叶皮层/下边缘皮层、杏仁核和伏隔核）中进行。目前的数据显示，母婴分离和社交挫败都显著影响了组蛋白甲基化以及β-连环蛋白、内源性阿片肽、神经生长因子和糖皮质激素信号通路中涉及的基因的表达。尽管母婴分离和社交挫败的影响在很大程度上没有重叠，但每个脑区中的一组基因受这些应激范式之间的加性、相反或其他类型的相互作用的控制，从而突出了这些应激源可能协调调节大脑功能和行为的潜在分子机制。
