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.