MiRNA-199a-5p targets WNT2 to regulate depression through the CREB/BDNF signaling in hippocampal neuron.

INTRODUCTION: This study mainly investigated the role of miR-199a-5p in depression. METHODS: qRT-PCR and western blotting were employed to detect the expressions of miR-199a-5p, CREB and BDNF. Sucrose preference test, forced swimming test, and tail suspension test were performed to evaluate depression-related symptoms. MTT assays and flow cytometry were used to examine the cell reproduction and apoptotic cells of hippocampal neuron. RESULTS: The data demonstrated that the expression levels of miR-199a-5p in the cerebrospinal fluids and serums of depression patient and the hippocampus of chronic unpredictable mild stress (CUMS) mouse were significantly increased. However, the expressions of WNT2, p-CREB, and BDNF were inhibited. In addition, miR-199a-5p-inhibitor enhanced sucrose preferences of CUMS mouse and decreased immobile time in sucrose preference test and forced swimming test. Knockdown of WNT2 attenuated the effects of miR-199a-5p-inhibitor on cell reproduction and apoptotic cells of hippocampal neuron and the expression of WNT2, p-CREB, and BDNF. CONCLUSION: MiR-199a-5p can target WNT2 to enhance the development of depression through regulation of the CREB/BDNF signaling. TRIAL REGISTRATION: JNU-Hos-49284.