| First Author | Xie L | Year | 2019 |
| Journal | Biochem Biophys Res Commun | Volume | 511 |
| Issue | 2 | Pages | 440-446 |
| PubMed ID | 30808545 | Mgi Jnum | J:291569 |
| Mgi Id | MGI:6443012 | Doi | 10.1016/j.bbrc.2019.02.078 |
| Citation | Xie L, et al. (2019) MicroRNA-26a-2 maintains stress resiliency and antidepressant efficacy by targeting the serotonergic autoreceptor HTR1A. Biochem Biophys Res Commun 511(2):440-446 |
| abstractText | The association between dysregulated serotonergic activity and major depressive disorder (MDD) is well known. However, the various mechanisms underlying serotonergic dysregulation in MDD remain unclear. Previous research on serotonergic (5-HT) neurons identified microRNA-26a (miR-26a) targeting of the serotonin autoreceptor, 5-HT receptor 1A (HTR1A). Reporter assays with the Htr1a 5'UTR sequence were performed in vitro. Adult transgenic mouse models altering miR-26a-2 and Htr1a expression were used for chronic social defeat, antidepressant treatment, and in vivo lentiviral experiments. Mice were tested for anxiety-like behavior using the elevated plus-maze, dark-light transfer, and open-field tests, and for depression-like behavior using the forced-swim test. We confirmed that miR-26a-2 downregulates Htr1a expression in 5-HT neurons in vitro. miR-26a-2 levels were significantly upregulated in the mouse dorsal raphe nucleus (DRN) following antidepressant therapy. The transgenic murine model overexpressing miR-26a-2 in serotonergic neurons displayed improved behavioral resiliency to social defeat. These effects were abrogated by the addition of Htr1a overexpression. In contrast, the transgenic murine model with miR-26a-2 knockdown in serotonergic neurons displayed increased anxious behavior and weakened antidepressant response. These effects were rescued by silencing Htr1a expression. Our findings suggest that miR-26a-2 functions as an endogenous antidepressant by targeting HTR1A in serotonergic neurons. |
