Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA.
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):503-514. doi: 10.1016/j.pnpbp.2017.08.009. Epub 2017 Aug 9.
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.
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，特别是在受伤后。然而，无论是在小鼠还是人类受试者中，miR-21 在成年 CNS 中的细胞表达都没有得到明确证实，而其在精神疾病中的改变尚不清楚。通过在表达内源性 miR-21 启动子（miR-21/LacZ）的报告小鼠中表达β-半乳糖苷酶（LacZ）来表征 miR-21 的表达。通过双免疫荧光在报告小鼠中检查 miR-21/LacZ 与特定神经标记物的脑共定位，同时在 miR-21 敲除和野生型小鼠中确定髓鞘碱性蛋白和 PDGFRα 的免疫染色程度。通过 qRT-PCR 测量人类受试者左眶额皮质（OFC）死后白质（WM）中 miR-21 的水平以及选定的 miR-21 靶标、miR-21 调节因子 STAT3 和髓鞘相关蛋白的 mRNA，患有重度抑郁症（MDD）、酗酒、合并 MDD 加酗酒（MDA）和非精神病对照受试者。miR-21/LacZ 在 WM 和灰质（GM）的有髓部分的细胞体中高度表达。标记的细胞体被鉴定为少突胶质细胞，而其他细胞类型中几乎检测不到 miR-21/LacZ。MDD 和酗酒受试者的 WM 中 miR-21 以及几种髓鞘相关蛋白的 mRNA 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。成年少突胶质细胞中 miR-21 的高表达以及 miR-21 减少与一些髓鞘蛋白、调节因子 STAT3 和少突胶质细胞相关转录因子的 mRNA 相关，表明 miR-21 参与了抑郁和酗酒的 WM 改变。
