Oldham Green Nicole, Maniam Jayanthi, Riese Jessica, Morris Margaret J, Voineagu Irina
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
Neurobiol Stress. 2021 Mar 10;14:100316. doi: 10.1016/j.ynstr.2021.100316. eCollection 2021 May.
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, 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 an increase in one of the behavioural measures of anxiety like-behaviours in rats (percent of entries in the EPM open arm). 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 observed across ELS protocols and replicable across rodent species (mouse and rat).
早期生活应激（ELS）与不良心理健康后果相关，包括焦虑、抑郁和成瘾样行为。虽然已知ELS会影响发育中的大脑，导致应激反应性增加和糖皮质激素水平升高，但ELS有害影响的分子机制仍未完全明确。啮齿动物模型在开始揭示ELS的分子和细胞基础方面发挥了重要作用。有限筑巢（LN）是一种比母婴分离有显著改进的ELS行为范式，模拟了人类母亲的忽视。我们之前已经表明，LN会导致大鼠焦虑样行为的一种行为指标增加（高架十字迷宫开放臂进入次数的百分比）。在这里，我们通过RNA测序评估了ELS在大鼠前额叶皮质中诱导的基因表达变化。我们表明，LN主要导致转录抑制，并在大鼠前额叶皮质中鉴定出LN的分子特征，这种特征在各种ELS实验方案中都能观察到，并且在啮齿动物物种（小鼠和大鼠）中具有可重复性。
