Department of Work Psychology and Physiology, National Institute of Occupational Health, Oslo, Norway.
Department of Biosciences, University of Oslo, Oslo, Norway.
Stress. 2020 Jan;23(1):77-86. doi: 10.1080/10253890.2019.1642320. Epub 2019 Jul 24.
Prolonged exposure to bullying behaviors may give rise to symptoms such as anxiety, depression and chronic pain. Earlier data suggest that these symptoms often are associated with stress-induced low-grade systemic inflammation. Here, using data from both animals and humans, we examined the moderating role of microRNAs (miRNAs, miRs) in this process. In the present study, a resident-intruder paradigm, blood samples, tissue harvesting and subsequent qPCR analyses were used to screen for stress-induced changes in circulating miRNAs in rats. The negative acts questionnaire (NAQ), TaqMan assays and a numeric rating scale (NRS) for pain intensity were then used to examine the associations among bullying behaviors, relevant miRNA polymorphisms and pain in a probability sample of 996 Norwegian employees. In rats, inhibited weight gain, reduced pituitary POMC expression, adrenal Nr3c1 mRNA downregulation, as well as increased miR-146a, miR-30c and miR-223 in plasma were observed following 1 week of repeated exposure to social stress. When following up the miRNA findings from the animal study in the human working population, a stronger relationship between NAQ and NRS scores was observed in subjects with the miR-30c GG genotype (rs928508) compared to other subjects. A stronger relationship between NAQ and NRS scores was also seen in men with the miR-223 G genotype (rs3848900) as compared to other men. Our findings show that social stress may induce many physiological changes including changed expression of miRNAs. We conclude that the miR-30c GG genotype in men and women, and the miR-223 G genotype in men, amplify the association between exposure to bullying behaviors and pain.Lay summaryUsing an animal model of social stress, we identified miR-146a, miR-30c and miR-223 as potentially important gene regulatory molecules that may be involved in the stress response. Interestingly, human genotypes affecting the expression of mature miR-30c and miR-223 had a moderating effect on the association between exposure to bullying and pain. Subjects with the miR-30c rs928508 GG genotype had a significantly stronger association between exposure to bullying behaviors and pain than other subjects. The same was observed in men with the miR-223 rs3848900 G genotype, as compared to other men.
长期遭受欺凌行为可能会导致焦虑、抑郁和慢性疼痛等症状。早期数据表明，这些症状通常与应激引起的低度系统性炎症有关。在这里，我们使用动物和人类的数据，研究了 microRNAs（miRNAs，miRs）在这一过程中的调节作用。在本研究中，使用居民入侵者范式、血液样本采集和随后的 qPCR 分析，筛选大鼠循环 miRNA 中应激诱导的变化。然后使用欺凌行为问卷（NAQ）、TaqMan 检测和疼痛强度数字评分量表（NRS），在挪威 996 名员工的概率样本中检验欺凌行为、相关 miRNA 多态性与疼痛之间的关联。在大鼠中，反复暴露于社会压力 1 周后，观察到体重增加抑制、垂体 POMC 表达减少、肾上腺 Nr3c1 mRNA 下调以及血浆中 miR-146a、miR-30c 和 miR-223 增加。当在人类工作人群中对动物研究中的 miRNA 发现进行随访时，与其他受试者相比，miR-30c rs928508 （GG 基因型）的受试者中 NAQ 和 NRS 评分之间的关系更强。与其他男性相比，miR-223 rs3848900 （G 基因型）的男性中，NAQ 和 NRS 评分之间的关系也更强。我们的研究结果表明，社会压力可能会引起许多生理变化，包括 miRNA 表达的改变。我们的结论是，女性和男性中的 miR-30c GG 基因型以及男性中的 miR-223 G 基因型，放大了暴露于欺凌行为与疼痛之间的关联。
非专业人士译文
长期遭受欺凌行为可能会导致焦虑、抑郁和慢性疼痛等症状。早期数据表明，这些症状通常与应激引起的低度系统性炎症有关。在这里，我们使用动物和人类的数据，研究了 microRNAs（miRNAs，miRs）在这一过程中的调节作用。在本研究中，使用居民入侵者范式、血液样本采集和随后的 qPCR 分析，筛选大鼠循环 miRNA 中应激诱导的变化。然后使用欺凌行为问卷（NAQ）、TaqMan 检测和疼痛强度数字评分量表（NRS），在挪威 996 名员工的概率样本中检验欺凌行为、相关 miRNA 多态性与疼痛之间的关联。在大鼠中，反复暴露于社会压力 1 周后，观察到体重增加抑制、垂体 POMC 表达减少、肾上腺 Nr3c1 mRNA 下调以及血浆中 miR-146a、miR-30c 和 miR-223 增加。当在人类工作人群中对动物研究中的 miRNA 发现进行随访时，与其他受试者相比，miR-30c rs928508 （GG 基因型）的受试者中 NAQ 和 NRS 评分之间的关系更强。与其他男性相比，miR-223 rs3848900 （G 基因型）的男性中，NAQ 和 NRS 评分之间的关系也更强。我们的研究结果表明，社会压力可能会引起许多生理变化，包括 miRNA 表达的改变。我们的结论是，女性和男性中的 miR-30c GG 基因型以及男性中的 miR-223 G 基因型，放大了暴露于欺凌行为与疼痛之间的关联。
