Zhan Yuhua, Han Jiyang, Xia Jing, Wang Xumei
Department of Psychiatry, Shengjing Hospital of China Medical University, Shenyang City, Liaoning Province, People's Republic of China.
Neuropsychiatr Dis Treat. 2021 Feb 22;17:613-626. doi: 10.2147/NDT.S289444. eCollection 2021.
Berberine has been found to inhibit the progression of depression disorder, but its specific mechanism is still unclear. MicroRNA (miRNA) is considered to play an important role in the progression of depression. However, it is unclear whether Berberine is involved in the regulation of depression progression through miRNA.
The chronic unpredictable mild stress (CUMS) mice model was constructed. Mice depression behaviors were evaluated by sucrose preference test (SPT) and forced swim test (FST). Quantitative real-time PCR was employed to assess the expression of miR-34b-5p, miR-470-5p and brain-derived neurotrophic factor (BDNF). The protein expression of BDNF was examined using Western blot analysis. In addition, the viability and apoptosis of hippocampal neurons were determined using cell counting kit 8 assay, flow cytometry and TUNEL assay. The interaction between BDNF and miR-34b-5p or miR-470-5p was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay.
Our data indicated that Berberine could inhibit CUMS mice depression behaviors and enhance hippocampal neurons growth by targeting miR-34b-5p and miR-470-5p. In addition, we found that BDNF was a target of miR-34b-5p and miR-470-5p. Overexpressed BDNF could reverse the regulation of miR-34b-5p and miR-470-5p on CUMS mice depression behaviors and hippocampal neurons growth. Furthermore, Berberine could promote BDNF expression to regulate CUMS mice depression behaviors and hippocampal neurons growth.
Berberine might inhibit the progression of depression disorder by regulating the miR-34b-5p/miR-470-5p/BDNF axis.
已发现小檗碱可抑制抑郁症的进展，但其具体机制仍不清楚。微小RNA（miRNA）被认为在抑郁症进展中起重要作用。然而，尚不清楚小檗碱是否通过miRNA参与抑郁症进展的调控。
构建慢性不可预测轻度应激（CUMS）小鼠模型。通过蔗糖偏好试验（SPT）和强迫游泳试验（FST）评估小鼠的抑郁行为。采用定量实时PCR评估miR-34b-5p、miR-470-5p和脑源性神经营养因子（BDNF）的表达。使用蛋白质印迹分析检测BDNF的蛋白表达。此外，使用细胞计数试剂盒8检测、流式细胞术和TUNEL检测确定海马神经元的活力和凋亡。通过双荧光素酶报告基因检测和RNA免疫沉淀检测验证BDNF与miR-34b-5p或miR-470-5p之间的相互作用。
我们的数据表明，小檗碱可通过靶向miR-34b-5p和miR-470-5p抑制CUMS小鼠的抑郁行为并促进海马神经元生长。此外，我们发现BDNF是miR-34b-5p和miR-470-5p的靶标。过表达BDNF可逆转miR-34b-5p和miR-470-5p对CUMS小鼠抑郁行为和海马神经元生长的调控。此外，小檗碱可促进BDNF表达以调节CUMS小鼠的抑郁行为和海马神经元生长。
小檗碱可能通过调节miR-34b-5p/miR-470-5p/BDNF轴抑制抑郁症的进展。
