Expression and role of microRNA-212/nuclear factor I-A in depressive mice

Abstract

Depression is characterized by persistent depressed mood and cognitive dysfunction, severely impacting human health. In the present study, we aimed to explore the role and mechanism of microRNA (miR)-212 in depression in vivo . Chronic unpredictable mild stress (CUMS) mice were established, and depression-like behaviors were confirmed using the forced swimming test (FST), sucrose preference test (SPT), and the tail suspension test (TST). Next, the expression of miR-212 and its potential target, i.e., nuclear factor I-A (NFIA), was verified using quantitative reverse transcription (qRT)-PCR analysis and Western blotting in CUMS mice. The effects of miR-212 and NFIA on depression-like behaviors, inflammatory response, and neuronal apoptosis were examined using FST, TST, SPT, enzyme-linked immunosorbent assay (ELISA) assay, and flow cytometry analysis. Finally, the relationship between miR-212 and NFIA was examined using a dual-luciferase reporter assay. Based on our findings, miR-212 was significantly upregulated, while NFIA was downregulated in CUMS mice. miR-212 overexpression could suppress the CUMS-induced weight loss, immobility time in FST and TST, and increased hippocampal neuronal apoptosis and pro-inflammatory cytokines levels. In addition, NFIA upregulation could partially reverse the effects of miR-212 mimic in CUMS mice. Accordingly, miR-212 could ameliorate CUMS-induced depression-like behavior in mice by targeting NFIA, indicating its protective role in depression.

MicroRNAs underlying the antidepressant effect of psilocybin – Establishing an nCounter pipeline for microRNA-quantification in the pig brain

“…This indicate that upregulation of miR-212-5p might be a protective compensatory mechanism in CUMS mice, rather than a pathological mechanism that needs to be corrected. In support of this assumption, Si et al ( 2021) provided evidence for neuroprotective and anti-in ammatory (reduced Tumor necrosis factor-alpha (TNF-α), Interleukin-1 beta, and Interleukin-6 levels) effects using miR-212-5p mimics in the CUMS mice 33 . Similarly, psilocybin has been reported to acutely decrease TNF-α levels in blood from healthy subjects, as TNF-α was reverted to baseline levels, one week after psilocybin administration 35 .…”

“…In the context of bladder cancer, it has been demonstrated with Targetscan predictions and luciferase assays that miR-212-3p also targets NFIA 34 , thus demonstrating that both miR-212-5p and miR-212-3p targets NFIA and may act through similar antidepressive molecular mechanisms. Interestingly, in a study by Si et al (2021), the depressivelike CUMS mice already exhibited elevated miR-212-5p levels in blood and HIP, but the antidepressant like effects were achieved through further over-expression of miR-212-5p 33 . This indicate that upregulation of miR-212-5p might be a protective compensatory mechanism in CUMS mice, rather than a pathological mechanism that needs to be corrected.…”

MicroRNA-139-5p acts as a suppressor gene for depression by targeting nuclear receptor subfamily 3, group C, member 1

“…Tail suspension test was conducted as previously reported [ 17 ]. A 15 cm long and 1.9 cm wide tape was positioned.…”

“…Forced swimming test was conducted as previously reported [ 17 ]. The experimental animals were placed in a resin glass tank with a height of 24 cm, a diameter of 12 cm, a water depth of 20 cm, and a water temperature of 25.2°C.…”

“…The human miR-139-5p gene at 11q13.4 [ 13 ] is poorly expressed in many diseases, and its expression indicates a poor prognosis [ 14 ]. Recent studies have shown that miR-139-5p has been identified as a potential depressive biomarker isolated from patients’ serum exosomes [ 15 , 16 ] and miR-212 might play a protective role in depression by regulating apoptosis and inflammatory responses in mouse hippocampal neurons [ 17 ]. However, no study have demonstrated the role of Mir-139-5p in hippocampal neurons.…”