Objective To explore the changes of circRIMS2 in mice with depression like behavior and the influence of circRIMS2 on oxygen-glucose deprivation (OGD) induced apoptosis of HT22 cells. Methods (1) Forty-five C57BL/6 female mice were randomly divided into the control group, model group,and fluoxetine group, with 15 mice in each group. A depression like behavior model was constructed in both the model group and fluoxetine group mice through chronic restraint stress (CRS), and fluoxetine group mice were treated with 10 mg/kg of fluoxetine. Depression like behavior in mice was evaluated using the sucrose preference test, tail suspension test, forced swimming test, and open field test. After evaluation, mouse serum and hippocampal tissue were collected, and the expression of circular RNA, miR-186, and BDNF mRNA were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). Western blot was used to detect the expression of BDNF protein in mice hippocampus. (2) After adding lentiviral vectors pLO-circCon and pLO-circRIMS2 transfection reagents to HT22 cells, a portion of HT22 cells were subjected to OGD treatment to construct an in vitro apoptosis model. Based on the cell transfection and OGD procedures, HT22 cells were divided into Control+pLO-circCon group, Control+pLO-circRIMS2 group, OGD+pLO-circCon group, and OGD+pLO-circRIMS2 group. RT-qPCR was used to detect the expression of circRIMS2, miR-186, and BDNF mRNA in four groups of cells, and flow cytometry was used to detect and calculate the apoptosis rate of the four groups of cells. Results (1) Compared with the control group, the model group mice had a lower preference for sucrose, longer tail suspension and forced immobility time, lower open field test scores, higher expression levels of circTRAM2, circTNIK, and circTFRC in serum, and lower expression levels of circDOCK4, circRIMS2, and circSTAG1, and the differences were statistically significant (all P < 0.01). Compared with the model group, the fluoxetine group mice had a higher preference for sucrose, shorter tail suspension and forced swimming immobility time, higher open field test scores, and higher level of circRIMS2 expression in serum, with statistical differences (all P < 0.01). (2) Compared with the Control+pLO-circCon group, the Control+pLO-circRIMS2 group had higher levels of circRIMS2 and BDNF mRNA expression, lower level of miR-186 expression, and lower cell apoptosis rate, with statistically significant differences (all P < 0.01). Compared with the OGD+pLO-circCon group, the OGD+pLO-circRIMS2 group had higher levels of circRIMS2 and BDNF mRNA expression, lower level of miR-186 expression, and lower cell apoptosis rate, with statistically significant differences (all P < 0.01). Conclusions The circRIMS2 gene is associated with depression like behavior in mice. The expression of circRIMS2 in the serum of mice with depression like behavior is reduced, and fluoxetine can increase the expression of circRIMS2. The lentiviral plasmid enhances the expression of circRIMS2 gene in cells and can alleviate OGD induced neuronal apoptosis through miR-186/ BDNF signaling.
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贾丽,魏东,梁路. circRIMS2靶向miR-186调控BDNF表达减轻CRS诱发的小鼠抑郁样行为[J].神经疾病与精神卫生,2024,24(2): DOI :10.3969/j. issn.1009-6574.2024.02.005.