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

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.