[Mechanism of electroacupuncture on hippocampal neuron regeneration in depression rats based on Wnt/β-catenin and Notch signaling pathway].

OBJECTIVES: To observe the effect of electroacupuncture (EA) on the proliferation of hippocampal neurons and Wnt/β-catenin and Notch signaling pathways in depression like behavior rats, so as to explore its mechanism underlying improvement of depression.

METHODS: SD rats were randomly divided into blank, model, medication and EA groups, with 12 rats in each group. The depression model was established by chronic unpredictable mild stimulation combined with solitary raising for 35 consecutive days. After 14 days modeling, EA was applied to "Baihui"(GV20) and "Taichong"(LR3) for 15 min once daily for 3 weeks. For rats of the medication group, clomipramine (2.5 mg/kg) was given (i.p.) once a day for 3 weeks. The depression-like behavior was evaluated by open field test and forced swimming test. The ultrastructure of hippocampal neurons was observed by transmission electron microscope (TEM). The positive expression of 5-bromo-2'-deoxyuridine/neuron-specific nucleoprotein (BrdU/NeuN) in hippocampal dentate gyrus of rats was detected by immunofluorescence double labeling method. Western blot was used to detect the relative expression of Wnt/β-catenin and Notch pathway key proteins β-catenin, G1/S-specific cyclin-D1 (Cyclin D1), NICD and Hes1 in hippocampus of rats.

RESULTS: Compared with the blank group, the total distance and average speed of open field movement were decreased (P<0.01), and the immobility time of forced swimming was increased (P<0.01). The positive expression of BrdU/NeuN in hippocampal dentate gyrus was decreased (P<0.01). The relative expression of β-catenin and Cyclin D1 protein in hippocampus were decreased (P<0.01), while the relative expression of NICD and Hes1 protein increased (P<0.01) in the model group. Following the treatment and compared with the model group, the total distance and average speed of movement in the open field were increased (P<0.05), and the immobility time of forced swimming was decreased (P<0.05) in both medication and EA groups. The positive expression of BrdU/NeuN in hippocampal dentate gyrus was increased (P<0.01). The relative expression of β-catenin and Cyclin D1 protein in hippocampus were increased (P<0.01), while the relative expression of NICD and Hes1 protein were decreased (P<0.01, P<0.05) in both medication and EA groups. TEM microscope observation showed irregularity of hippocampal neurons, rupture of nuclear membranes, disruption of mitochondrial structure, and dilation of endoplasmic reticulum in the model group, which was relatively milder in both medication and EA groups.

CONCLUSIONS: EA can improve the depressive state of depression model rats, which may be associated with its functions in regulating Wnt and Notch signaling pathways, thereby promoting the regeneration of hippocampal neurons.