Gsk - 3 Beta Gene Expression In The Role Of Depressive Disorder Behavior Patterns Before And After The Treatment

Objective:To use animal models of depression, transgenic mice with the Glycogen synthase kinase-3β(GSK-3β) over-expressed,and they were grouped by chronic unpredictable mild stress (CMS) or fluoxetine or not.The acute phases of intervention and long term were undertaken on the basis of treatment allocation., to compare the difference between groups in depressed behavior, to find out the correlation between the damage of cells in mice hippocampal and depressed behavior, and to explore the relationship between GSK-3β and the development of depression.Methods:1.40C57BL/6J mice were randomly divided into five groups, according to chronic unpredictable mild stress (CMS) or fluoxetine or not, normal group (contributor), GSK3β over-expression group (Lvx-GSK3β),over-expression GSK3β group with CMS (Lvx-GSK3β+CMS), over-expression GSK3β group with fluoxetine (Lvx-GSK3β+fluoxetine),over-expression GSK3β group with CMS and fluoxetine (Lvx-GSK3β+CMS+fluoxetine).2. The acute phases of intervention:the group with fluoxetine was injected only once with fluoxetine (20mg/kg), the group with non-fluoxetine was injected only once with saline wate (20mg/kg),30minutes later, the forced swimming test and tail suspension test were used to evaluate the depressed behavior.3. The long term intervention:the group with fluoxetine was injected with fluoxetine (12mg/kg/d), the group with non fluoxetine was injected with saline wate (12mg/kg/d),14days later, the forced swimming test and tail suspension test were also used to evaluate the depressed behavior, the mice were killed, brain tissues from the brain and hippocampal gyrus were sliced into frozen sections.the apoptosis and proliferation of neural precursor cells were observed by immunofluorescence.Then, all the collected data was analyzed by SPSS16.0for data statistics and analysis.Results:1. The acute phases of intervention,the immobility time of the forced swimming test and tail suspension test:LVX-GSK3β group and Lvx-GSK3β+CMS group showed obviously to be longer than normal control groups (P<0.05), Lvx-GSK3β+CMS group showed obviously to be longer than LVX-GSK3β group (P<0.05), But it is not found differences between GSK3β+CMS+fluoxetine group and LVX-GSK3β.(P>0.05), T test showed no corresponding difference between LVX-GSK3β+CMS+fluoxetine group and LVX-GSK3β+CMS (P>0.05)2. The long term intervention, the immobility time of the forced swimming test and tail suspension test:Lvx-GSK3β+fluoxetine group showed significantly to be shorter than LVX-GSK3β group (P<0.05),.LVX-GSK3β+CMS group show significantly to be shorter than LVX-GSK3β+CMS+fluoxetine group (P<0.01), LVX-GSK3β+CMS+fluoxetine group showed significantly to be longer than Lvx-GSK3β+fluoxetine group (P<0.01),But T test showed no corresponding difference between Lvx-GSK3β+fluoxetine and normal controls (P>0.05), it is not found differences between LVX-GSK3β+CMS+fluoxetine group and normal controls (P>0.05)3.The results from immunofluorescence:GFP (green),TUNEL positive cells in the hippocampal. gyrusdentatus zone was calculated under a fluorescent microscope:The number of apoptotic cells in LVX-GSK3β group was more than in normal controls,(P<0.01), The number of apoptotic cells in Lvx-GSK3β+CMS group was more than in LVX-GSK3β group (P <0.05), Lvx-GSK3β+fluoxetine group showed significantly to be less than LVX-GSK3β group (P<0.01),and the same result was showed between LVX-GSK3β+CMS+fluoxetine group and LVX-GSK3β+CMS group (P<0.01); The fluorescence intensity was observed in DAPI staining, a true measure of the viable cells. The number of the viable cells in LVX GSK3β group was less than in normal controls,(P<0.01), The number of the viable cells in Lvx-GSK3β+CMS group was less than in LVX-GSK3β group (P<0.05), Lvx-GSK3β+fluoxetine group showed significantly to be more than LVX-GSK3β group (P<0.01),and the same result was showed between LVX-GSK3β+CMS+fluoxetine group and LVX-GSK3p+CMS group (P<0.01)Conclusion:1. GSK-3β may be linked to the development of depression.2. CMS may be one of the important factors affecting prognosis.3. GSK-3β may be take part in the regulation of the hippocampal synaptic plasticity in mice. Objective:Major depressive disorder has been linked to alterations in the multifunctional enzyme glycogen synthase kinase-3β (GSK-3β). The antidepressant medicines inhibit GSK-3β in vitro and in mice brain,we tested whether fluoxetine modified GSK-3β in vivo in peripheral blood mononuclear cells (PBMCs) from healthy control and major depressive disorder subjects, and to explore the relationship between GSK-3β and the development of depressive disorder.Methods:1. A case control study and prospective study were conducted., the PBMCs were obtained from17major depressive disorder subjects and17healthy control subjects matched for age and sex, major depressive disorder subjects were treated with fluoxetine therapy for8weeks.2.Immunoblot analyses were used to measure GSK-3β and the inhibited, serine9-phosphorylated GSK-3p.Results:1. The level of GSK-3β was increased in major depressive disorder subjects, compared to healthy controls (p=0.006), the level of GSK-3β was decreased by in vivo fluoxetine treatment.(p=0.039), but GSK-3β levels between fluoxetine treatment group and healthy controls was no corresponding difference (p>0.05)2. Phos-pho-Ser9-GSK3β levels were higher in PBMCs from fluoxetine-treated major depressive disorder subjects than before the treatment (p=0.027) and healthy controls (p=0.015).Conclusion:1.GSK-3β may be linked to the development of depressive disorder.2.Signaling pathways regulating serine9-phosphorylation of GSK-3β is associated with depressive disorder.3.fluoxetine treatment is associated with a large increase in phospho-Ser9-GSK-3β in PBMCs,the inhibitory serine9-phosphorylation of GSK-3β in human PBMCs may provide a biochemical marker to evaluate the association between GSK-3β inhibition and therapeutic responses to fluoxetine treatment.