MicroRNA-21: Expression in oligodendrocytes and correlation with low myelin mRNAs in depression and alcoholism.

MicroRNA-21: Expression in oligodendrocytes and correlation with low myelin mRNAs in depression and alcoholism.
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MicroRNA-21:少突胶质细胞中的表达及其与抑郁症和酗酒中低髓磷脂 mRNA 的相关性。

DOI:
10.1016/j.pnpbp.2017.08.009
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发表时间:
2017-10-03
影响因子:
5.6
通讯作者:
Romero DG
Romero DG
中科院分区:
医学2区
文献类型:
--
作者:
Miguel-Hidalgo JJ;Hall KO;Bonner H;Roller AM;Syed M;Park CJ;Ball JP;Rothenberg ME;Stockmeier CA;Romero DG

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miR-21是一种与癌症、发育和心血管疾病有关的microRNA,在中枢神经系统(CNS)中表达,尤其是在损伤后。然而,miR-21在成年CNS中的细胞表达在小鼠或人类受试者中均未明确确立,而其在精神疾病中的改变尚不清楚。在内源性miR-21启动子(miR-21/LacZ)下表达β-半乳糖苷酶(LacZ)的报告小鼠中表征miR-21表达。在报告小鼠中通过双重免疫荧光检查了miR-21/LacZ与特定神经标志物的脑共定位,而在miR-21敲除小鼠和野生型小鼠中测定了髓鞘碱性蛋白和PDGFRα的免疫染色程度。通过qRT-PCR测量了患有重度抑郁症(MDD)、酒精中毒、MDD+酒精中毒共病(MDA)的人类受试者和非精神病对照受试者的左侧死后眶额皮质(OFC)附近的白色物质(WM)中miR-21和选定的miR-21靶标、miR-21调节剂STAT 3和髓鞘相关蛋白的mRNA水平。MiR-21/LacZ在WM的细胞体和灰质(GM)的有髓鞘部分中高度表达。标记的细胞体被鉴定为少突胶质细胞,而miR-21/LacZ在其他细胞类型中几乎检测不到。MiR-21以及几种髓鞘相关蛋白的mRNA在患有MDD和酒精中毒的受试者的WM中减少。miR-21与髓鞘相关蛋白和星形胶质细胞GFAP的mRNA呈正相关。miR-21在成年少突胶质细胞中的高表达以及miR-21的减少与一些髓鞘蛋白、调节因子STAT 3和少突胶质细胞相关转录因子的mRNA的相关性表明miR-21参与抑郁症和酒精中毒的WM改变。
MiR-21 is a microRNA implicated in cancer, development, and cardiovascular diseases and expressed in the central nervous system (CNS), especially after injury. However, the cellular expression of miR-21 in the adult CNS has not been clearly established either in mice or human subjects, while its alteration in psychiatric disorders is unknown. MiR-21 expression was characterized in reporter mice expressing β–galactosidase (LacZ) under the endogenous miR-21 promoter (miR-21/LacZ). Brain co-localization of miR-21/LacZ with specific neural markers was examined by double immunofluorescence in reporter mice, while extent of immunostaining for myelin basic protein and PDGFRα was determined in miR-21 knockout and wild-type mice. Levels of miR-21, and mRNAs of selected miR-21 targets, miR-21 regulator STAT3 and myelin-related proteins were measured by qRT-PCR in the white matter (WM) adjacent to the left postmortem orbitofrontal cortex (OFC) of human subjects with major depressive disorder (MDD), alcoholism, comorbid MDD plus alcoholism (MDA) and non-psychiatric control subjects. MiR-21/LacZ was highly expressed in cell bodies of WM and myelinated portions of gray matter (GM). Labeled cell bodies were identified as oligodendrocytes, while miR-21/LacZ was barely detectable in other cell types. MiR-21, as well as the mRNAs of several myelin-related proteins, were reduced in the WM of subjects with MDD and alcoholism. MiR-21 positively correlated with mRNA of myelin-related proteins and astrocytic GFAP. High expression of miR-21 in adult oligodendrocytes and the correlation of miR-21 decrease with mRNA of some myelin proteins, regulator STAT3, and oligodendrocyte-related transcription factors suggest an involvement of miR-21 in WM alterations in depression and alcoholism.
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