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.

Automated summary

The study found that miR-199a-5p expression levels were significantly increased in the cerebrospinal fluids and serums of depression patients as well as in the hippocampus of chronic unpredictable mild stress (CUMS) mice. However, the expressions of WNT2, p-CREB, and BDNF were inhibited. In addition, the miR-199a-5p inhibitor enhanced certain behaviors associated with depression in CUMS mice, and this effect was attenuated by knockdown of WNT2.