Effects Of Huazhuo Jiedu Shugan Formula On Learning And Memory And Expression Of NCAM,GAP-43 And PKC In Depression Mice

Objective: To investigate the effect and possible mechanism of Huazhuo Jiedu Shugan Formula on depression-like behavior and learning and memory ability of chronic unpredictability mild stress(CUMS)model mice,and to provide experimental evidence for the clinical application of Huazhuo Jiedu Shugan Formula.Methods: Forty-eight ICR mice were randomly divided into control group,model group,the low,medium and high dose group of Huazhuo Jiedu Shugan Formula(low,medium and high dose group)and fluoxetine group(8 mice per group).In addition to the control group,the other mice replicated the CUMS model of depression,which consisted of 14 stimuli,given two different stimuli each day for 21 days,without repetition,each day of the week.The body mass of mice was weighed every week.During the modeling,15 m L/kg of normal saline was given to the control group and the model group every day,0.85 g/kg,1.7 g/kg and 3.4 g/kg were given to the low,medium and high groups,and 10mg/kg was given to the fluoxetine group.The volume of gavage fluid per unit volume is the same.Depression-like behavior and learning and memory were measured by sugar preference test,body weight,morris water maze and radial arm maze.Western blot and immunohistochemistry were used to detect the expression of NCAM,GAP-43 and PKC in hippocampus.Result:1.Test results for depression-like behavior and learning and memory(1)The sucrose preference score in model group was lower than that in control group(P<0.01).The sucrose preference score in the high,medium and fluoxetine groups(P<0.01)and the low group(P<0.05)was higher than that in the model group.(2)Body weight measurement results: on the 14 th day of the experiment,the body weight of mice in the model group was lower than that in the control group(P<0.01),and the body weight of mice in the high group and fluoxetine group was higher than that in the model group(P<0.01).On the 21 st day of the experiment,the body weight of the model group was lower than that of the control group(P<0.01),the body weight of the high group and the fluoxetine group(P<0.01)and the medium group(P<0.05)was higher than that of the model group.(3)Morris water maze test results show:In the place navigation,the escape latency of the model group was significantly longer than that of the control group(P<0.01),while the escape latency of the high group(P<0.01),fluoxetine group(P<0.01)and medium group(P<0.05)was shorter than that of the model group.In the spatial probe test,the number of crossing times of mice in the model group was significantly lower than that in the control group(P<0.01),the number of crossing times in the high group(P<0.01)and fluoxetine group(P<0.05)was significantly higher than that in the model group.In the reverse platform experiment,the reverse platform incubation period of mice in the model group was longer than that in the control group(P<0.01),while the reverse platform incubation period of mice in the high,medium and fluoxetine groups was shorter than that in the model group(P<0.01).(4)In the radial arm maze experiment,the working and reference memory errors of mice in the model group were higher than those in the control group(P<0.01),the working and reference memory errors of mice in the high and fluoxetine groups were lower than those in the model group(P<0.01).2.Immunohistochemical test results:The integrated optical density values of the hippocampus CA1,CA3,DG region NCAM,GAP-43 and PKC in the model group were significantly lower than those in the control group(P<0.01),while the integrated optical density values of the hippocampus CA1,CA3,DG region NCAM,GAP-43 and PKC in the high group and fluoxetine group were significantly higher than those in the model group(P<0.05).3.Western blot test results:The expression levels of NCAM,GAP-43 and PKC in the model group were lower than those in the cotrol group(P<0.01),while the expression levels of NCAM,GAP-43 and PKC in the high,medium,low and fluoxetine groups were significantly higher than those in the model group(P<0.01).Conclusion:1.In the model mice of depression,there was a learning and memory disorder,accompanied by changes in the expression of NCAM,GAP-43 and PKC proteins in the hippocampus.2.The improvement of depression may be related to the up-regulated expression of NCAM,GAP-43 and PKC in hippocampus.3.Huazhuo Jiedu Shugan Formula has application and development value as a prescription for prevention and treatment of depression,which is equivalent to that of fluoxetine.