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

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 79; no. Pt B; pp. 503 - 514
• Main Authors: Miguel-Hidalgo, José Javier, Hall, Katherine O., Bonner, Hannah, Roller, Anna M., Syed, Maryam, Park, Casey J., Ball, Jana P., Rothenberg, Marc E., Stockmeier, Craig A., Romero, Damian G.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 03.10.2017
• Subjects: Alcoholism - complications; Alcoholism - epidemiology; Alcoholism - metabolism; Alcoholism - pathology; Animals; Astrocytes; Comorbidity; Depressive Disorder, Major - complications; Depressive Disorder, Major - epidemiology; Depressive Disorder, Major - metabolism; Depressive Disorder, Major - pathology; Female; Glia; Gray Matter - metabolism; Gray Matter - pathology; Human; Humans; Knockout; Male; Mice, Inbred C57BL; Mice, Transgenic; MicroRNAs - metabolism; Middle Aged; miR-21; Mouse; mRNA; Myelin Basic Protein - metabolism; Myelin Sheath - metabolism; Oligodendroglia - metabolism; Postmortem; Prefrontal; Prefrontal Cortex - metabolism; Prefrontal Cortex - pathology; Receptor, Platelet-Derived Growth Factor alpha - metabolism; RNA, Messenger - metabolism; STAT3 Transcription Factor - metabolism; White Matter - metabolism; White Matter - pathology; Human; Mouse; Astrocytes; Prefrontal; Postmortem; mRNA; miR-21; Glia; Knockout
• ISSN: 0278-5846; 1878-4216; 1878-4216
• DOI: 10.1016/j.pnpbp.2017.08.009

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. [Display omitted] •miR-21 is highly expressed in adult oligodendrocytes.•miR-21 level in orbitofrontal white matter is low in depression and alcoholism.•miR-21 correlates with low mRNA of PLP1, transcription factor OLIG1 and STAT3.•miR-21 may be implicated in the white matter pathology of depression and alcoholism.