Department of Psychiatry, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Eur Rev Med Pharmacol Sci. 2020 Feb;24(3):1398-1407. doi: 10.26355/eurrev_202002_20197.
To study the influence of micro ribonucleic acid (miR)-155 on depression-like behaviors of depression mice, and to explore the role of Wnt/b-catenin signaling pathway in behavioral regulation of depression mice.
The mouse model of depression was established via chronic unpredictable mild stress (CUMS). All mice were randomly divided into control group (n=12), model group (n=12), and fluoxetine group (n=12). The expression level of miR-155 in the hippocampus of mice in each group was detected via quantitative Polymerase Chain Reaction (qPCR). The changes in the behaviors of mice in each group were evaluated via behavioral experiments. The apoptosis level in the hippocampus of mice in each group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Moreover, the content of inflammatory factors in the hippocampus of mice in each group was detected using the enzyme-linked immunosorbent assay (ELISA) kits. The expression levels of Wnt/b-catenin signaling pathway-related proteins in each group were detected via Western blotting.
The expression level of miR-155 in the hippocampus was significantly higher in model group than that in control group (p<0.01). Meanwhile, the expression level of miR-155 was significantly lower in fluoxetine group than that in model group (p<0.01). There were no statistically significant differences in the crossing score and rearing score in the open field test among groups (p>0.05). Compared with those in control group, the immobility time in tail suspension test and forced swimming test were significantly increased (p<0.01), while the sucrose preference degree significantly declined (p<0.01) in model group. Fluoxetine could significantly reduce the immobility time in tail suspension test and forced swimming test (p<0.01) and increase the sucrose preference degree (p<0.01) in model group. The number of TUNEL-positive cells in the hippocampus of mice in model group was significantly larger than that in control group (p<0.01). Fluoxetine could effectively reduce the number of TUNEL-positive cells in the hippocampus (p<0.01). Compared with those in control group, the content of tumor necrosis factor-α (TNF-a), interleukin-1b (IL-1b), and IL-6 in the hippocampus was significantly increased (p<0.01), while the content of IL-10 was significantly decreased (p<0.01) in model group. Fluoxetine could effectively reduce the content of TNF-a, IL-1b, and IL-6 (p<0.01) and increase the content of IL-10 (p<0.01). Besides, in model group, the expression levels of dishevelled-1 (DVL-1) and b-catenin in hippocampus remarkably declined (p<0.01), while the expression levels of glycogen synthase kinase-3b (GSK-3b) and adenomatous polyposis coli (APC) were remarkably increased (p<0.01) compared with those in control group. Fluoxetine could effectively lower the expressions of GSK-3b and APC in the hippocampus (p<0.01) and increase the expressions of DVL-1 and b-catenin (p<0.01) in model group.
MiR-155 is involved in regulating the depression-like behaviors of depression mice through promoting the release of inflammatory factors and the apoptosis of hippocampal neurons. Its mechanism may be related to the inhibition of the Wnt/b-catenin signaling pathway.
研究微小 RNA-155（miR-155）对抑郁小鼠抑郁样行为的影响，探讨 Wnt/β-连环蛋白信号通路在抑郁小鼠行为调节中的作用。
采用慢性不可预知性轻度应激（CUMS）建立小鼠抑郁模型。所有小鼠随机分为对照组（n=12）、模型组（n=12）和氟西汀组（n=12）。采用实时定量聚合酶链反应（qPCR）检测各组小鼠海马组织中 miR-155 的表达水平。采用行为学实验评估各组小鼠的行为变化。采用末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）染色检测各组小鼠海马组织的凋亡水平。此外，采用酶联免疫吸附试验（ELISA）试剂盒检测各组小鼠海马组织中炎症因子的含量。采用 Western blot 检测各组小鼠海马组织中 Wnt/β-连环蛋白信号通路相关蛋白的表达水平。
模型组小鼠海马组织中 miR-155 的表达水平明显高于对照组（p<0.01）。同时，氟西汀组小鼠海马组织中 miR-155 的表达水平明显低于模型组（p<0.01）。各组在旷场实验中的穿越分数和直立分数无统计学差异（p>0.05）。与对照组相比，模型组小鼠在悬尾试验和强迫游泳试验中的不动时间明显增加（p<0.01），而糖水偏好程度明显降低（p<0.01）。氟西汀可明显降低模型组小鼠在悬尾试验和强迫游泳试验中的不动时间（p<0.01），并增加糖水偏好程度（p<0.01）。模型组小鼠海马组织中 TUNEL 阳性细胞数明显多于对照组（p<0.01）。氟西汀可有效减少海马组织中 TUNEL 阳性细胞数（p<0.01）。与对照组相比，模型组小鼠海马组织中肿瘤坏死因子-α（TNF-α）、白细胞介素-1b（IL-1b）和 IL-6 的含量明显增加（p<0.01），而 IL-10 的含量明显降低（p<0.01）。氟西汀可有效降低 TNF-α、IL-1b 和 IL-6 的含量（p<0.01），并增加 IL-10 的含量（p<0.01）。此外，在模型组中，海马组织中的 DVL-1 和 β-连环蛋白表达水平明显下降（p<0.01），而 GSK-3b 和 APC 的表达水平明显升高（p<0.01）。氟西汀可有效降低海马组织中 GSK-3b 和 APC 的表达水平（p<0.01），并增加 DVL-1 和 β-连环蛋白的表达水平（p<0.01）。
miR-155 通过促进炎症因子的释放和海马神经元的凋亡参与调节抑郁小鼠的抑郁样行为，其机制可能与抑制 Wnt/β-连环蛋白信号通路有关。
