Improving Effect Of Human Umbilical Cord Mesenchymal Stem Cell Transplantation On Depression Behavior In Chronic Stress Model Mice

Objective:To investigate the effects of human umbilical cord mesenchymal stem cells(hUCMSCs)transplanted into tail vein into chronic unpredictable mild stress(CUMS)model mice on the improvement of depressive behavior.Methods:Firstly,the third generation of hUCMSCs was obtained after purchasing and subculturing.Secondly,60 male C57BL/6 mice were randomly divided into four groups:normal group,model group(+ normal saline),cell group(+ hUCMSCs)and drug group(+ flu),with 15 mice in each group.The depression model of 6-week CUMS mice was established.From the third week,hUCMSCs and normal saline were transplanted into mice by caudal vein injection.From the fifth week,fluoxetine(flu)was given to mice every day by the means of gavage.The body weight of mice in each group was recorded every week.The depression degree and the therapeutic effect of hUCMSCs and flu were evaluated by sucrose preference test,tail suspension test,forced swimming test and open field test in normal group and mice model made by CUMS procedure.After that,the structure and cell changes of hippocampal CA1 and CA3 region were observed by HE staining.After the preliminary results were obtained,the changes of synapses in the CA3 region of hippocampus of four groups were detected by transmission electron microscopy.Finally,the m RNA expression levels of synaptophysin(SYP)and postsynaptic density protein 95(PSD-95),a key protein for synaptic plasticity,were detected by real-time PCR.Results:The subcultured hUCMSCs showed typical mesenchymal stem cell morphology under inverted microscope.hUCMSCs could improve the body weight loss in mice caused by CUMS procedure.In the behavioral experiment,depressive behavior was observed in the model group,meanwhile which was improved in the cell group and the drug group.HE staining results showed that,compared with the model group,cells in the hippocampus CA1 and CA3 region of mice in the cell group and the drug group were more orderly and the number of cells was increased.Compared with the model group,the number of subcellular synapses in the hippocampal CA3 region in the cell group and the drug group was more,the synaptic gap was narrower,and the density of synaptic spines was higher.Real-time PCR detected more m RNA expression of SYP and PSD-95 in the cell group and the drug group than in the model group.Conclusion:hUCMSCs exhibited resistance to depressive behavior of mice experienced CUMS procedure,and this effect was related to the improvement of synaptic plasticity in the hippocampus of CUMS mice.