Silence of MiR-9 protects depression mice through Notch signaling pathway

Z.-Y. Ma, F. Chen, P. Xiao, X.-M. Zhang, X.-X. Gao

Department of Psychiatry, Jining Psychiatric Hospital, Jining, China. xiaopjsk@yeah.net

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• Pharmacology

OBJECTIVE: To investigate the potential influence of micro ribonucleic acid (miR)-9 on depressive behaviors of depression mice.
MATERIALS AND METHODS: Depression model in mice was established via chronic unpredictable mild stress. A total of 36 C57BL/6 mice were randomly divided into control group (control mice, n=12), model group (depression mice administrated with control lentivirus, n=12) and miR-9 low-expression group (depression mice administrated with LV-miR-9-shRNA lentivirus, n=12). After 6 weeks, the depressive behaviors of mice were evaluated by behavioral experiments. Mice were then sacrificed for harvesting the hippocampus. Relative level of miR-9 in mouse hippocampus was determined via quantitative polymerase chain reaction (qPCR). Moreover, the number of newborn neurons in the hippocampus in each group was detected via immunofluorescence assay. Expression levels of doublecortin (DCX), post-synaptic density protein 95 (PSD95) and Notch signaling pathway in the hippocampus in each group were detected via Western blotting.
RESULTS: In the open field test, there were no significant differences in the crossing score and rearing score among control group, model group and miR-9 low-expression group (p>0.05). The immobility time of mice in tail suspension test and forced swimming test increased significantly in model group compared with that in control group (p<0.01), while it was significantly shorter in miR-9 low-expression group than that in model group (p<0.01). The expression of miR-9 in mouse hippocampus in model group was significantly higher than that in control group and miR-9 low-expression group (p<0.01). In miR-9 low-expression group, the number of newborn neurons in the hippocampus was significantly larger than that in control group and model group (p<0.01). Protein levels of both DCX and PSD95 were significantly higher in control group than those in model group (p<0.01). Besides, protein levels of Notch intracellular domain (NICD), Hes1 and Jag1 in the hippocampus in model group were remarkably declined compared with those in control group (p<0.01), which were higher in miR-9 low-expression group.
CONCLUSIONS: MiR-9 is upregulated in the hippocampus of depression mice. Silence of miR-9 in the hippocampus can effectively activate the Notch signaling pathway, promote the neuronal regeneration in the hippocampus and improve the depressive symptoms of mice.

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