Early life stress leads to gene expression down-regulation in prefrontal cortex [microarray]

Early life stress (ELS) is associated with adverse mental health outcomes including anxiety, depression and addiction-like behaviours. While ELS is known to affect the developing brain by leading to increased stress responsiveness and increased glucocorticoid levels, the molecular mechanisms underlying the detrimental effects of ELS remain incompletely characterised. Rodent models have been instrumental in beginning to uncover the molecular and cellular underpinnings of ELS. Limited nesting (LN), an ELS behavioural paradigm with significant improvements over maternal separation, mimics human maternal neglect. We have previously shown that LN leads to anxiety like-behaviours in rats. Here we assessed gene expression changes induced by ELS in rat prefrontal cortex by RNA-sequencing. We show that LN leads primarily to transcriptional repression and identify a molecular signature of LN in rat PFC that is robust to the behavioural paradigm and replicable across rodent species (mouse and rat).早期生活压力（Early Life Stress，ELS）与包括焦虑、抑郁及类成瘾行为在内的多种不良心理健康结局相关。尽管已知早期生活压力可通过增强应激反应性、升高糖皮质激素水平影响发育中的大脑，但其有害效应背后的分子机制仍未得到充分阐释。啮齿类动物模型在揭示早期生活压力的分子与细胞基础方面发挥了至关重要的作用。有限筑巢（Limited Nesting，LN）作为一种较母体分离法更具优势的早期生活压力行为范式，可模拟人类的母体忽视行为。我们此前的研究已证实，有限筑巢会使大鼠产生类焦虑行为。本研究通过RNA测序（RNA-sequencing）技术，检测了早期生活压力诱导的大鼠前额叶皮层基因表达变化。结果表明，有限筑巢主要引发转录抑制，并在大鼠前额叶皮层中鉴定出该行为范式特异性的分子特征，该特征具有良好的稳健性，且可在小鼠与大鼠等啮齿类物种间重复验证。