P-CREB1Expression Level And The Ultrastructure Of Neuron And Synapse In Hippocampus Of Depression Rats

BackgroundThe hippocampus researches have demonstrated that depression behaviors are associated with the reduced expression of p-CREB1(phospho cAMP response element-binding protein1) and the changing of neuronal activity and synaptic plasticity. It is still not fully understood how they result in depression. This project try to explore a potential nosogenesis by study the expression of p-CREB1, the ultrastructure of neuron and synapse in the hippocampus of depression rats, and their changes after pharmacotherapy.Objectives1. To investigate the expression of p-CREB1protein and mRNA in rat hippocampus of each group, and the change after treatment.2. To observe the ultrastructure of neuron and synapse in the hippocampus of depression rats.3. To investigate the learning and memory ability and behavior of depression rats among normal group, depression model group and medication group.Methods1. Rats were divided into normal group (n=12) and model group (n=42). To establish the depression rat model by chronic unpredictable mild stress. Model group were divided into three groups, and they are depression model matched group (n=14), depression model and saline group (n=14), depression model and medication group (n=14).2. To detect the behavior of rats by body weight measurement, sucrose water consumption test and open field test. To test the learning and memory ability of rats by Morris water maze.3. To detect the expression of p-CREB1protein by Immunohistochemistry; and to detect the expression of CREB1mRNA by RT-PCR (reverse transcription and polymerase chain reaction).4. To observe the ultrastructure of neuron and synapse in the hippocampus of depression rats by EMS (electron microscope).Results1. Behavior results:There were significant differences between normal group and depression model group in weight (t=2.172, P<0.05), sucrose consumption (t=3.306, P<0.01), run-up time of open field test (t=-3.568, P<0.01), horizontal behavior(t=2.330, P<0.05) and vertical behavior(t=2.147, P<0.05). All of them demonstrated that the depression model had been established successfully. After pharmacotherapy, the behavior comparison of four groups:weight (F=40.009, P<0.01), sucrose consumption (F=17.851, P<0.01), run-up time of open field test(F=35.319, P<0.01), horizontal behavior(F=7.509, P<0.01) and vertical behavior(F=11.970, P<0.01). Morris water maze place navigation (Fday1=1.817, P>0.05; Fday7=30.559, P<0.01); spatial probe (Fdistance=14.154, P<0.01; traversing times=31.198, P<0.01; Ftime=34.185, P<0.01); these results demonstrated the learning and memory abilities of depression rats had decreased, and they can be improved by pharmacotherapy.2. Immunohistochemical results:Positive cell number of p-CREB1in the hippocampus of depression rats (FCA1=16.497, P<0.01; FCA3=23.494, P<0.01; FDG=37.628, P<0.01); Positive cells integral light density(FCA1=26.659, P<0.01; FCA3=4.466, P<0.01; FDG=6.158, P<0.01)3. RT-PCR results:The p-CREB1mRNA expression (F=6.669, P<0.01). The p-CREB1mRNA expression of depression rats was lower than normal group (P<0.05); medication group was higher than depression rats (P<0.01). 4. Electron microscope results:That the ultrastructure of neuron and synapse in the hippocampus of depression rats suffered pathological changes, and pharmacotherapy can make them improve. Synaptic morphological parameters comparison:Synaptic number (F=3.983, P<0.05), Synaptic activity length (F=8.848, P<0.01), postsynaptic density (F=18.896, P<0.01)Conclusions1. The rat model of depression has been established successfully, and the venlafaxine intervention has improved the behavior performance of depression model rats.2. The learning and memory abilities of depression rats were declined, and pharmacotherapy can improve them.3. The expression of p-CREB1in the hippocampus of depression rats was reduced, and pharmacotherapy can help it rise.4. That the ultrastructure of neuron and synapse in the hippocampus of depression rats suffered pathological changes, and pharmacotherapy can make them improve.5. Our findings suggest that p-CREB1play an important role both in attack and in the treatment of depression, and it may bring effect through impact the neuronal and sympatric plasticity.