miR-149 and miR-29c as Candidates for Bipolar Disorder Biomarkers
miR-149 and miR-29c as Candidates for Bipolar Disorder Biomarkers
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DOI：
10.1002/ajmg.b.32518
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发表时间：
2017-04-01
影响因子：
2.8
通讯作者：
Delalle, Ivana
中科院分区：
文献类型：
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作者：
Choi, Jason L.;Kao, Patricia F.;Delalle, Ivana
双相情感障碍（BD）是一种常见的、复发性精神疾病，其发病机制尚不清楚。最近的研究表明，BD患者大脑中的microRNA（miRNA）水平显著改变，这些变化可能提供对BD病理学或病因学的见解。先前，我们观察到从BD患者的前额叶皮层（Brodmann区9，BA 9）提取的细胞外囊泡（EV）中的miR-29 c水平的显著改变。在这项研究中，我们表明，与对照组相比，从前扣带皮层（BA 24）提取的EV（调节情绪表达和情感的关键区域）增加了BD患者的miR-149水平。由于miR-149已显示出抑制神经胶质细胞增殖，因此BA 24衍生EV中miR-149表达增加与先前报道的诊断为家族性BD或家族性重度抑郁症的患者BA 24中神经胶质细胞数量减少一致。来自BD患者的BA 24皮质样品的激光显微切割的神经元和神经胶质细胞的qPCR分析证实神经胶质而非神经元群体表现出显著增加的miR-149表达。最后，我们报告了从Flinders Sensitive Line大鼠脑中提取的EV中miR-149和miR-29 c的表达改变，Flinders Sensitive Line大鼠是一种经过充分验证的动物模型，表现出抑郁样行为和神经胶质（星形胶质细胞）功能障碍。这些发现保证了未来研究使用EV miRNA签名作为生物标志物的潜力，以进一步提高BD的生物学定义。(C)2017 Wiley Periodicals，Inc.
Bipolar disorder (BD) is a common, recurring psychiatric illness with unknown pathogenesis. Recent studies suggest that microRNA (miRNA) levels in brains of BD patients are significantly altered, and these changes may offer insight into BD pathology or etiology. Previously, we observed significant alterations of miR-29c levels in extracellular vesicles (EVs) extracted from prefrontal cortex (Brodmann area 9, BA9) of BD patients. In this study, we show that EVs extracted from the anterior cingulate cortex (BA24), a crucial area for modulating emotional expression and affect, have increased levels of miR-149 in BD patients compared to controls. Because miR-149 has been shown to inhibit glial proliferation, increased miR-149 expression in BA24-derived EVs is consistent with the previously reported reduced glial cell numbers in BA24 of patients diagnosed with either familial BD or familial major depressive disorder. qPCR analysis of laser-microdissected neuronal and glial cells from BA24 cortical samples of BD patients verified that the glial, but not neuronal, population exhibits significantly increased miR-149 expression. Finally, we report altered expression of both miR-149 and miR-29c in EVs extracted from brains of Flinders Sensitive Line rats, a well-validated animal model exhibiting depressive-like behaviors and glial (astrocytic) dysfunction. These findings warrant future investigations into the potential of using EV miRNA signatures as biomarkers to further enhance the biological definition of BD. (C) 2017 Wiley Periodicals, Inc.