Psychology Department, Qingdao Mental Health Center, Qingdao University, Qingdao City, Shandong Province, China.
Pharmacy Department, Qingdao Women and Children's Hospital, Qingdao City, Shandong Province, China.
Bioengineered. 2022 May;13(5):11856-11866. doi: 10.1080/21655979.2022.2059937.
MicroRNA-139-5p (miR-139-5p) is one of the most differentially expressed miRNAs in the brain between healthy people and depressed patients. However, its function in depression is unclear. Therefore, we investigated the function of miR-139-5p in depression. Here, miR-139-5p expression was found to be upregulated in the model group. MiR-139-5p inhibition could increase sucrose preference and decrease mice immobility time after chronic corticosterone (CORT) injection. Furthermore, compared with the antago-NC group, 3 weeks of antagomiR-139-5p treatment significantly decreased miR-139-5p level in model group hippocampus, increased sucrose preference index, reduced neuron damages, and enhanced the levels of nuclear receptor subfamily 3 group C member 1 (NR3C1), brain-derived neurotrophic factor (BDNF), phosphorylated/total tyrosine kinase receptor B (p-TrkB/TrkB), phosphorylated/total cAMP-response element-binding protein (p-CREB/CREB) and phosphorylated/total extracellular regulated protein kinases (p-ERK/ERK). Moreover, as a potential target for miR-139-5p, NR3C1 level was reduced by miR-139-5p mimic. Altogether, by activating the BDNF-TrkB signaling pathway, miR-139-5p inhibition plays an antidepressant-like role and might serve as an effective depression target (Fig. graphical abstract).
微小 RNA-139-5p（miR-139-5p）是健康人与抑郁患者大脑中差异表达最多的 miRNA 之一。然而，其在抑郁症中的功能尚不清楚。因此，我们研究了 miR-139-5p 在抑郁症中的功能。研究发现，miR-139-5p 在模型组中表达上调。慢性皮质酮（CORT）注射后，miR-139-5p 抑制可增加蔗糖偏好，减少小鼠不动时间。此外，与 antago-NC 组相比，3 周的 antagomiR-139-5p 处理可显著降低模型组海马 miR-139-5p 水平，增加蔗糖偏好指数，减少神经元损伤，并增强核受体亚家族 3 组 C 成员 1（NR3C1）、脑源性神经营养因子（BDNF）、磷酸化/总酪氨酸激酶受体 B（p-TrkB/TrkB）、磷酸化/总 cAMP 反应元件结合蛋白（p-CREB/CREB）和磷酸化/总细胞外调节蛋白激酶（p-ERK/ERK）水平。此外，作为 miR-139-5p 的潜在靶标，NR3C1 水平被 miR-139-5p 模拟物降低。总之，通过激活 BDNF-TrkB 信号通路，miR-139-5p 抑制发挥抗抑郁样作用，可能成为一种有效的抑郁靶点（图。摘要）。
