Antidepressant Effect Of Zhiju Jieyu Decoction On Depressive Model Mice And Its Neural Mechanism

Objective: Used multivariate chronic unpredicted mild stress(CUMS) to build depression model mice and examined the neurobehavioral changes including mice weight, open filed behavior, tail suspension test, sucrose consumption measurement and the spatial learning memory ability changes. Examined the changes of morphological structure and the expression of SDF-1 in hippocampus(HP) and prefrontal cortex(PFC) of mice brain. This study aims to explore the antidepressant effects and neural mechanisms of Chinese herbal compound of Zhijujieyu-tang acting on depression model mice from the perspectives of behavior biology and molecular neurobiology.Methods: Young mice were randomly divided into 6 groups including control group, model group, the fluoxetine group(positive drug group), Zhijujieyu-tang low dose group, medium dose group, high dose group. Depression mice model were established by using CUMS stress way,Distilled water, fluoxetine and different concentration of Zhijujieyu-tang given to the control group and the model group mice, fluoxetine group and the each Chinese herbal compound group by intragastric injection( i.g.) in every day, respectively.In the process of 21 days chronic stress,different groups of mice were measured regularly weight change. After chronic stress, using the open field test, tail suspension test and Morris water maze experiment to explore the change of spontaneous behavior, despair degree, spatial learning and memory ability of different group mice. Before and after chronic stress used sucrose consumption test to measure the change of anhedonia. Using HE staining method and Immunohistochemical(IHC) method to observe the morphology structure changes and the expression changes of SDF-1 in HF and PFC of mice brain.Result: 1.Weight changes. Compared with the control group, the weight of model group growth slows, after the stress significantly reduced. Compared with the model group mice, the weight of fluoxetine group and Zhijujieyu-tang medium dose group increased significantly. The weights of every dose group of Zhijujieyu-tang increased significantly.2. Open field test. Compared with the control group, under the environment of extraneous the model group reduced the exploration and spontaneous activity, increased tensity obviously.Compared with the model group mice, open field behavior of the fluoxetine group and every dose group of Zhijujieyu-tang had significant changes, including that the exploration and spontaneous activity increased significantly and tensity decreased obviously in fluoxetine group and medium dose group.3. Tail suspension test. Compared with the control group, the latency immobility and immobility time of the model group mice were significantly increased, indicated the desperate degree obviously increased. Compared with the model group mice, the latency immobility and immobility time were significantly reduced in fluoxetine group and Zhijujieyu-tang medium,high dose group, indicated the desperate degree reduced.4. Sucrose consumption measurement. Before chronic stress the sucrose consumption degree of every group had no significant difference. After CUMS stress, compared with the control group, the degree of sucrose consumption significantly reduced in the model group. Compared with the model group, the sucrose consumption of fluoxetine group and every dose group of Zhijujieyu-tang mice increased, indicating the degree of anhedonia reduced.5. Morris water maze. Compared with the control group mice, the escape latency of the model group mice increased obviously and the total swimming distance obviously prolonged in the place navigation test; in the spatial probe the resident time of target quadrant remarkable test significantly shortened, dropping through the platform decreased. Compared with the model group, the escape latency and the total swimming distance of fluoxetine group and every dose group of Zhijujieyu-tang mice were decreased significantly. The resident time of target quadrant remarkable increased obviously, and the number of times through the platform increased, that enhancing the ability of learning and memory.6. HE staining. In the model group the neurons of HP and PFC showed nucleus contraction,loose irregular and disorder arranged. Deformation cells appeared apoptosis phenomenon and the number of cells decrease, dyeing shallow and color uneven on neurons. The neuron of Fluoxetine group and every dose group of Zhijujieyu-tang mice(especially the medium dose group) in HP and PFC arranged orderliness, dyeing uniformity, and had no deformation cell.7. IHC of SDF-1. Compared with the control group mice, the number of SDF-1 positive neurons reduced remarkably and the average gray scale value of SDF-1 positive neurons significantly increased in HP and PFC of model group mice. The number of SDF-1 positive neurons increased and the gray scale value of SDF-1 positive neurons reduced obviously in HP and PFC of Fluoxetine group and every dose group of Zhijujieyu-tang mice, indicating that the expression of SDF-1 increased.Conclusions: 1. Depression model mice occurred many neurobehavioral changes. Chinese herbal compound of Zhijujieyu-tang can markedly improve the changes of neurobehavioral induced by chronic stress in mice, and that it have a certain antidepressant effect.2. Spatial learning and memory ability of the stress model mice significantly reduced. Chinese herbal compound of Zhijujieyu-tang can enhance the spatial learning and memory ability of model mice.3. In HP and PFC of the depression model mice neurons appeared different degree of damage,the expression of SDF-1 decreased. Chinese herbal compound of Zhijujieyu-tang can reduce the damage degree and have certain antidepressant effect, that its mechanism may be through increasing the expression of SDF-1 to reduce the damage of various brain regions.