title: miR-149 and miR-29c as candidates for bipolar disorder biomarkers.
abstract: 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. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Choi
authors.affiliation: Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Patricia F
authors.initials: PF
authors.lastname: Kao
authors.affiliation: Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Elena
authors.initials: E
authors.lastname: Itriago
authors.affiliation: Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Yougen
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Broad Institute, Cambridge, Boston, Massachusetts.|Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: James A
authors.initials: JA
authors.lastname: Kozubek
authors.affiliation: Department of Neurology, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Hoss
authors.affiliation: Advanced Tissue Resource Center, Harvard NeuroDiscovery Center, Charlestown, Massachusetts.
authors.forename: Meredith G
authors.initials: MG
authors.lastname: Banigan
authors.affiliation: Advanced Tissue Resource Center, Harvard NeuroDiscovery Center, Charlestown, Massachusetts.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Vanderburg
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Rezvani
authors.affiliation: Department of Neurology, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Jeanne C
authors.initials: JC
authors.lastname: Latourelle
authors.affiliation: Department of Biostatistics, Boston University School of Public Health and Boston University Clinical and Translational Science Institute, Boston, Massachusetts.
authors.forename: Howard
authors.initials: H
authors.lastname: Cabral
authors.affiliation: Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Ivana
authors.initials: I
authors.lastname: Delalle
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000235:genetics*; D001921:Brain / Q000473:pathology; D003865:Major Depressive Disorder / Q000473:pathology; D004195:Disease Models, Animal; D000067128:Extracellular Vesicles / Q000235:genetics; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D051381:Rats
chemical_list: D015415:Biomarkers; C551557:MIRN149 microRNA, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs
keywords: bipolar disorder; cingulate cortex; extracellular vesicles; miRNA; prefrontal cortex; qPCR