miR-323a regulates ERBB4 and is involved in depression.

TitlemiR-323a regulates ERBB4 and is involved in depression.
Publication TypeJournal Article
Year of Publication2020
AuthorsFiori LM, Kos A, Lin R, Théroux J-F, Lopez JPablo, Kühne C, Eggert C, Holzapfel M, Huettl R-E, Mechawar N, Belzung C, Ibrahim EChérif, Chen A, Turecki G
JournalMol Psychiatry
Date Published2020 Nov 20
ISSN1476-5578
Abstract

Major depressive disorder (MDD) is a complex and debilitating illness whose etiology remains unclear. Small RNA molecules, such as micro RNAs (miRNAs) have been implicated in MDD, where they display differential expression in the brain and the periphery. In this study, we quantified miRNA expression by small RNA sequencing in the anterior cingulate cortex and habenula of individuals with MDD and psychiatrically-healthy controls. Thirty-two miRNAs showed significantly correlated expression between the two regions (False Discovery Rate < 0.05), of which four, miR-204-5p, miR-320b, miR-323a-3p, and miR-331-3p, displayed upregulated expression in MDD. We assessed the expression of predicted target genes of differentially expressed miRNAs in the brain, and found that the expression of erb-b2 receptor tyrosine kinase 4 (ERBB4), a gene encoding a neuregulin receptor, was downregulated in both regions, and was influenced by miR-323a-3p in vitro. Finally, we assessed the effects of manipulating miRNA expression in the mouse ACC on anxiety- and depressive-like behaviors. Mice in which miR-323-3p was overexpressed or knocked-down displayed increased and decreased emotionality, respectively. Additionally, these mice displayed significantly downregulated and upregulated expression of Erbb4, respectively. Overall, our findings indicate the importance of brain miRNAs in the pathology of MDD, and emphasize the involvement of miR-323a-3p and ERBB4 in this phenotype. Future studies further characterizing miR-323a-3p and neuregulin signaling in depression are warranted.

DOI10.1038/s41380-020-00953-7
Alternate JournalMol Psychiatry
PubMed ID33219358
Grant ListFDN148374, FRN 141899, ENP161427 / / Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) /
EGM141899 / / Fonds de Recherche du Québec - Santé (Fonds de la recherche en sante du Quebec) /
ANR-15-EPIG-0003-03 / / Agence Nationale de la Recherche (French National Research Agency) /
ANR-15-EPIG-0003-03 / / Agence Nationale de la Recherche (French National Research Agency) /
01KU1504 / / Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) /