Effects Of Chronic Unpredictable Stress And Antidepressants On The Levels Of Ca～(2+)/Calmodulin-dependent Protein Kinase Ⅱ In The Rat Hippocampus

PrefaceDepression is the most popular kind of psychical disease. It has a higher recurrent rate and lifetime morbidity. There is growing evidence from neuroimag-ing and postmortem studies that severe mood disorders are associated with impairments of structural plasticity and cellular resilience. The damage of hipp-ocampal neuron is the key part in plasticity regulation of synapse and play a critical role in the mechanism of depression. Chronic stress can cause damage to brain, especially to the structure and the function of hippocampus, ultimately leads to the onset of depression. Ca²⁺ /Calmodulin -dependent protein kinase â…¡/CaMPK â…¡ is closely associated with neuron plasticity. In accordance with documents, we make the rats expose to stress for 3 weeks to manufacture the depression model. Meanwhile different antidepressants are given to the rats, to reveal the relationship of chronic stress, antidepressants, CaMPK â…¡ , neuron plasticity and depression.Materials1. Animals;40 male young Wistar rats.2. Reagents: Mouse anti rat a — CAMPK II monoclonal antibody( Chemi-con);Goat anti mouse IgG antibody ( Beijing Zhongshan Co. );DAB Kits( Beijing Zhongshan Co. ).3. Apparatus;YSD - 4 electronic stimulus instrument, Electrophoresis bath (BIO - RAD,U. S. A) , Electrophoresis apparatus, transfer apparatus ( Bei-jing six - one equipment factory) , Computer image analysis system ( Olympus, Japan).Methods1. According to Open - field, 40 rats were randomly divided into the control group ( CG);depression group ( DG);lithium group ( LG) and tianeptine group (TG). There are 10 rats in each group.2. The experimental group rats randomly accepted different stimulus for 21 days to get depressive model rats, and all rats were taken Open - field test again on the 22nd day. Then kill all the rats.3. Antidepressans were given to the rats by mouths each day before stress as bellows:CG(10) DG(10) LG(10) TG(10)Execution NS stress+ NS stress + lithium stress + tianeptine4. The levels of a — CaMPK II were detected by Western blotting.Results1. The weight and the numbers of field segments entered of depression group were obviously lower then the control group.2. The levels of a - CAMPK II in DG and LG were obviously lower than the control group. The a - CAMPK II levels in the tianeptine group had no diffrence with the control group. Furthermore, the a - CAMPK H expression in lithium group was even lower than the depression group.DiscussionThis study use chronic unpredictable stress of middle intension to make depressive model rats. According to the results of Open - field test, the weight andthe activity of experimental group were obviously lower than the control group, so the model is successful.Recent ten years depression research focus on neuron plasticity and resilience, a - CaMPK II is an important substance which can affect neuron plasticity. A lot of animal models research inform us, a - CaMPK H is an early and a-lert marker of harmful stimulation to brain or other organs, and is also important component element of antidepressants.The main substrate of a - CaMPK II are AMPA and Map2 in postsynaptic neurons. In postsynaptic neurons, activated a — CaMPK II can increase the expression of AMPA receptors and then transfer to postsynaptic membrane. Then will influence synaptic plasticity. Another way is Map2, a - CaMPK II can phosphorate Map2,and the latter have interaction with microbules through microtu-bule protein,then influence the synaptic plasticity.As a special antidepressant, tianeptine plays its antidepressant effect mainly through improving synaptic plasticity. In present the levels of a - CaMPK II in tianeptine group was no deffrent from control group, this inform us that tianeptine may play its antidepressant effect by upregulating a - CaMPK II ? While lithium group a - CaMPK II levels are even lower than depression group, this inform us maybe lithium decrease the expression ofa — CaMPK II.Conclusion1. Chronic unpredictable stresses cause rats losing weight and decrease the research and modify behaviors, and decrease the expression of a - CaMPK II.2. a - CaMPK II can improve the neuron plasticity in hippocampus. Tianeptine ' s effect of improving neuron plasticity may come from a - CaMPK H ?3. Lithium may decrease the expression of a - CaMPK H , but precisely proves should be researched next.