Infant circulating MicroRNAs as biomarkers of effect in fetal alcohol spectrum disorders.
Infant circulating MicroRNAs as biomarkers of effect in fetal alcohol spectrum disorders.
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婴儿循环MicroRNA作为胎儿酒精谱系障碍的生物标志物
DOI：
10.1038/s41598-020-80734-y
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发表时间：
2021-01-14
影响因子：
4.6
通讯作者：
Jacobson JL
中科院分区：
文献类型：
--
作者：
Mahnke AH;Sideridis GD;Salem NA;Tseng AM;Carter RC;Dodge NC;Rathod AB;Molteno CD;Meintjes EM;Jacobson SW;Miranda RC;Jacobson JL
产前酒精暴露（PAE）可导致认知和行为障碍以及生长缺陷。由于酒精相关的神经行为缺陷可能发生在没有明显的畸形特征或生长缺陷的情况下，因此需要确定可以预测神经行为损伤的PAE生物标志物。在这项研究中，我们评估了从重度暴露的开普敦队列中获得的婴儿血浆细胞外循环miRNA（exmiRNAs），以确定这些是否可用于预测PAE相关的生长受限和认知障碍。以吸烟作为协变量，PAE改变了27%的表达exmiRNAs，具有临床相关效应量（Cohen's d ≥ 0.4）。此外，在2周时，PAE增加了exmiRNAs在染色体上的相关表达，表明了潜在的协同调节。在验证性因素分析中，在2周和6.5个月时PAE改变的exmiRNAs表达的方差最好用三因素模型描述。通路分析发现，2周时的因子与（F1）细胞成熟、细胞周期抑制和体细胞生长相关，（F2）细胞存活、凋亡、心脏发育和代谢相关，（F3）细胞增殖、骨骼发育、造血和炎症相关，而在6.5个月时，与（F1）神经发育、神经嵴/中胚层衍生物发育和生长相关，（F2）免疫系统和炎症，和（F3）躯体生长和心血管发育。第2周的因子F3和第6.5个月的因子F2部分介导了PAE诱导的生长缺陷，第2周的因子F3部分介导了PAE对第6.5个月婴儿识别记忆的影响。这些研究结果表明，婴儿exmiRNA可以帮助识别在生长和认知方面表现出CAE相关缺陷的婴儿。
Prenatal alcohol exposure (PAE) can result in cognitive and behavioral disabilities and growth deficits. Because alcohol-related neurobehavioral deficits may occur in the absence of overt dysmorphic features or growth deficits, there is a need to identify biomarkers of PAE that can predict neurobehavioral impairment. In this study, we assessed infant plasma extracellular, circulating miRNAs (exmiRNAs) obtained from a heavily exposed Cape Town cohort to determine whether these can be used to predict PAE-related growth restriction and cognitive impairment. PAE, controlling for smoking as a covariate, altered 27% of expressed exmiRNAs with clinically-relevant effect sizes (Cohen’s d ≥ 0.4). Moreover, at 2 weeks, PAE increased correlated expression of exmiRNAs across chromosomes, suggesting potential co-regulation. In confirmatory factor analysis, the variance in expression for PAE-altered exmiRNAs at 2 weeks and 6.5 months was best described by three-factor models. Pathway analysis found that factors at 2 weeks were associated with (F1) cell maturation, cell cycle inhibition, and somatic growth, (F2) cell survival, apoptosis, cardiac development, and metabolism, and (F3) cell proliferation, skeletal development, hematopoiesis, and inflammation, and at 6.5 months with (F1) neurodevelopment, neural crest/mesoderm-derivative development and growth, (F2) immune system and inflammation, and (F3) somatic growth and cardiovascular development. Factors F3 at 2 weeks and F2 at 6.5 months partially mediated PAE-induced growth deficits, and factor F3 at 2 weeks partially mediated effects of PAE on infant recognition memory at 6.5 months. These findings indicate that infant exmiRNAs can help identify infants who will exhibit PAE-related deficits in growth and cognition.
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DOI：
10.1111/acer.13504
发表时间：
2017-12
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1097/01.alc.0000156125.50577.ec
发表时间：
2005-03-01
影响因子：
3.2
作者：
Burden, MJ;Jacobson, SW;Jacobson, JL
通讯作者：
Jacobson, JL
BAF（BRG1/BRM相关因子）染色质复合物在胎儿神经祖细胞中表现出乙醇敏感性，并调节MiR-9-2编码基因基因座的转录。
DOI：
10.1016/j.alcohol.2017.01.003
发表时间：
2017-05
期刊：
Alcohol (Fayetteville, N.Y.)
影响因子：
--
作者：
Burrowes SG;Salem NA;Tseng AM;Balaraman S;Pinson MR;Garcia C;Miranda RC
通讯作者：
Miranda RC
DOI：
10.1111/j.1530-0277.2012.01793.x
发表时间：
2012-10
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Balaraman S;Winzer-Serhan UH;Miranda RC
通讯作者：
Miranda RC
DOI：
10.1111/j.2044-8317.1950.tb00285.x
发表时间：
1950-06-01
期刊：
BRITISH JOURNAL OF PSYCHOLOGY-STATISTICAL SECTION
影响因子：
--
作者：
Bartlett, M. S.
通讯作者：
Bartlett, M. S.