压力放大了灵长类动物前额叶基因表达的性别差异。
Stress amplifies sex differences in primate prefrontal profiles of gene expression.
机构信息
Department of Psychiatry and Behavioral Sciences, Stanford University, 1201 Welch Rd MSLS Room P104, Stanford, CA, 94305-5485, USA.
Molecular and Behavioral Neuroscience Institute and Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
出版信息
Biol Sex Differ. 2017 Nov 2;8(1):36. doi: 10.1186/s13293-017-0157-3.
BACKGROUND
Stress is a recognized risk factor for mood and anxiety disorders that occur more often in women than men. Prefrontal brain regions mediate stress coping, cognitive control, and emotion. Here, we investigate sex differences and stress effects on prefrontal cortical profiles of gene expression in squirrel monkey adults.
METHODS
Dorsolateral, ventrolateral, and ventromedial prefrontal cortical regions from 18 females and 12 males were collected after stress or no-stress treatment conditions. Gene expression profiles were acquired using HumanHT-12v4.0 Expression BeadChip arrays adapted for squirrel monkeys.
RESULTS
Extensive variation between prefrontal cortical regions was discerned in the expression of numerous autosomal and sex chromosome genes. Robust sex differences were also identified across prefrontal cortical regions in the expression of mostly autosomal genes. Genes with increased expression in females compared to males were overrepresented in mitogen-activated protein kinase and neurotrophin signaling pathways. Many fewer genes with increased expression in males compared to females were discerned, and no molecular pathways were identified. Effect sizes for sex differences were greater in stress compared to no-stress conditions for ventromedial and ventrolateral prefrontal cortical regions but not dorsolateral prefrontal cortex.
CONCLUSIONS
Stress amplifies sex differences in gene expression profiles for prefrontal cortical regions involved in stress coping and emotion regulation. Results suggest molecular targets for new treatments of stress disorders in human mental health.
背景
压力是情绪和焦虑障碍的公认风险因素，女性比男性更容易出现这些障碍。前额皮质区域介导压力应对、认知控制和情绪。在这里，我们研究了性别的差异以及压力对成年松鼠猴前额皮质基因表达谱的影响。
方法
在应激或无应激处理条件下，从 18 只雌性和 12 只雄性松鼠猴的背外侧、腹外侧和腹内侧前额皮质区域收集样本。使用为松鼠猴定制的 HumanHT-12v4.0 Expression BeadChip 芯片获取基因表达谱。
结果
在前额皮质区域中，许多常染色体和性染色体基因的表达存在广泛的差异。在前额皮质区域中，大多数常染色体基因的表达也存在明显的性别差异。与雄性相比，雌性表达增加的基因在丝裂原激活蛋白激酶和神经营养因子信号通路中过度表达。与雄性相比，雌性表达增加的基因数量较少，并且没有确定分子途径。与无应激条件相比，应激条件下腹内侧和腹外侧前额皮质区域的性别差异的效应量更大，但背外侧前额皮质区域则不然。
结论
应激放大了参与压力应对和情绪调节的前额皮质区域的基因表达谱中的性别差异。结果为人类心理健康中应激障碍的新治疗方法提供了分子靶点。
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