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首页> 美国卫生研究院文献>Frontiers in Psychiatry >Sex-Specific and Strain-Dependent Effects of Early Life Adversity on Behavioral and Epigenetic Outcomes
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Sex-Specific and Strain-Dependent Effects of Early Life Adversity on Behavioral and Epigenetic Outcomes

机译：早期逆境对行为和表观遗传结果的性别特异性和应变依赖性影响

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Early life adversity can have a significant long-term impact with implications for the emergence of psychopathology. Disruption to mother-infant interactions is a form of early life adversity that may, in particular, have profound programing effects on the developing brain. However, despite converging evidence from human and animal studies, the precise mechanistic pathways underlying adversity-associated neurobehavioral changes have yet to be elucidated. One approach to the study of mechanism is exploration of epigenetic changes associated with early life experience. In the current study, we examined the effects of postnatal maternal separation (MS) in mice and assessed the behavioral, brain gene expression, and epigenetic effects of this manipulation in offspring. Importantly, we included two different mouse strains (C57BL/6J and Balb/cJ) and both male and female offspring to determine strain- and/or sex-associated differential response to MS. We found both strain-specific and sex-dependent effects of MS in early adolescent offspring on measures of open-field exploration, sucrose preference, and social behavior. Analyses of cortical and hippocampal mRNA levels of the glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf) genes revealed decreased hippocampal Bdnf expression in maternally separated C57BL/6J females and increased cortical Bdnf expression in maternally separated male and female Balb/cJ offspring. Analyses of Nr3c1and Bdnf (IV and IX) CpG methylation indicated increased hippocampal Nr3c1 methylation in maternally separated C57BL/6J males and increased hippocampal Bdnf IX methylation in male and female maternally separated Balb/c mice. Overall, though effect sizes were modest, these findings suggest a complex interaction between early life adversity, genetic background, and sex in the determination of neurobehavioral and epigenetic outcomes that may account for differential vulnerability to later-life disorder.
机译：早期生活逆境可能会对精神病理学的产生产生重大的长期影响。母婴互动的中断是一种早期逆境的形式，尤其可能对发育中的大脑产生深远的编程影响。然而，尽管来自人类和动物研究的证据不断增多，但与逆境相关的神经行为改变的确切机制仍待阐明。研究机理的一种方法是探索与早期生活经历相关的表观遗传变化。在当前的研究中，我们检查了小鼠中产后母体分离（MS）的作用，并评估了这种操作在后代中的行为，脑基因表达和表观遗传学作用。重要的是，我们包括了两种不同的小鼠品系（C57BL / 6J和Balb / cJ）以及雄性和雌性后代，以确定与MS相关的与菌株和/或性别相关的差异反应。我们发现，在青春期后代中，MS的菌株特异性和性别依赖性效应对开放野外探索，蔗糖偏爱和社会行为的影响。糖皮质激素受体（Nr3c1）和脑源性神经营养因子（Bdnf）基因的皮质和海马mRNA水平分析显示，在母体分离的C57BL / 6J女性中，海马Bdnf表达降低，而在母体分离的男女Balb / cJ中，皮质Bdnf表达增加。后代。对Nr3c1和Bdnf（IV和IX）CpG甲基化的分析表明，母本分离的C57BL / 6J雄性小鼠海马Nr3c1甲基化增加，母本和母本分离的Balb / c小鼠海马Bdnf IX甲基化增加。总体而言，尽管影响大小适中，但这些发现表明，在确定神经行为和表观遗传学结局时，早期生活逆境，遗传背景和性别之间存在复杂的相互作用，这可能是导致晚年生活障碍的差异性脆弱性的原因。

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