Abstract：
Early-life adversity (ELA) causes long-lasting structural and functional changes to the brain, rendering affected individuals vulnerable to the development of psychopathologies later in life. Immediate-early genes (IEGs) provide a potential marker for the observed alterations, bridging the gap between activity-regulated transcription and long-lasting effects on brain structure and function. Several heterogeneous studies have used IEGs to identify differences in cellular activity after ELA; systematically investigating the literature is therefore crucial for comprehensive conclusions. Here, we performed a systematic review on 39 pre-clinical studies in rodents to study the effects of ELA (alteration of maternal care) on IEG expression. Females and IEGs other than cFos were investigated in only a handful of publications. We meta-analyzed publications investigating specifically cFos expression. ELA increased cFos expression after an acute stressor only if the animals (control and ELA) had experienced additional hits. At rest, ELA increased cFos expression irrespective of other life events, suggesting that ELA creates a phenotype similar to naïve, acutely stressed animals. We present a conceptual theoretical framework to interpret the unexpected results. Overall, ELA likely alters IEG expression across the brain, especially in interaction with other negative life events. The present review highlights current knowledge gaps and provides guidance to aid the design of future studies.
摘要：
早期逆境（ELA）会导致大脑长期的结构和功能变化，使受影响的个体在以后的生活中容易受到精神病理学的发展。立即早期基因（IEG）为观察到的改变提供了潜在的标记，弥合活性调节转录与对大脑结构和功能的长期影响之间的差距。一些异质性研究已经使用IEG来鉴定ELA后细胞活性的差异;因此，系统地研究文献对于综合结论至关重要。这里,我们对39项啮齿类动物临床前研究进行了系统评价,以研究ELA(母体护理改变)对IEG表达的影响.只有少数出版物对cFos以外的女性和IEG进行了调查。我们荟萃分析了专门研究cfos表达的出版物。只有当动物(对照和ELA)经历了额外的命中时,ELA才在急性应激源后增加cFos表达。在休息时,ELA增加cfos表达，与其他生活事件无关，这表明ELA创造了一种类似于天真的表型，极度紧张的动物。我们提出了一个概念性的理论框架来解释意想不到的结果。总的来说,ELA可能会改变整个大脑的IEG表达，尤其是与其他负面生活事件的互动。本综述强调了当前的知识差距，并为未来研究的设计提供了指导。
