Berberine Suppresses Mice Depression Behaviors and Promotes Hippocampal Neurons Growth Through Regulating the miR-34b-5p/miR-470-5p/BDNF Axis

Yuhua Zhan, Jiyang Han, Jing Xia, Xumei Wang Department of Psychiatry, Shengjing Hospital of China Medical University, Shenyang City, Liaoning Province, People’s Republic of ChinaCorrespondence: Xumei WangDepartment of Psychiatry, Shengjing Hospital of China Medical University, Shenyang City, Liaoning Province, People’s Republic of ChinaTel/Fax +86 0249-661566112Email xiaoyema2020@163.comBackground: 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.Methods: 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.Results: 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.Conclusion: Berberine might inhibit the progression of depression disorder by regulating the miR-34b-5p/miR-470-5p/BDNF axis.Keywords: depression disorder, Berberine, miR-34b-5p, miR-470-5p, BDNF