Effect Of Zhijiang Jieyu Decoction On Learning And Memory And Expression Of NCAM In Depressed Mice

In this study, we used multivariate chronic unpredicted mild stress(High platform, foot shock, oblique cage experiment, food deprivation, water deprivation, cold stimulation, all-night lighting) to establish the animal model of depression. Stress lasts for 21 days, adopt gastric lavage give the various group animal Chinese herbal compound of Zhijujieyu-tang and single substance drug immature bitter orange(IBO) and acorus gramineus soland( AGS). The young mice were divided into the control group, the model group, the fluoxetine group, the medium concentration of Zhijujieyu-tang group, the IBO group, and the AGS group. Used open field testing spontaneous activity and exploratory behavior in mice, and tail suspension test was used to detect the changes of mood and behavior in mice. The spatial learning memory ability was examined in mice by using Morris water maze tests. After the end of behavioral testing, enzyme activity assay was used to detect the changes of CAT and MAO activity in the hippocampus(HP)and prefrontal cortex(PFC) of mice, HE staining was performed to observe the changes of neurons in HP and PFC of the mice from the morphological; To detect the expression of neural cell adhesion molecule(NCAM) in various brain regions of HP and PFC in mice by immunohistochemistry test; To explore the antidepressant effect and mechanism of Chinese herbal compound of Zhijujieyu-tang.Experimental results:1. Open field test: Compared with the control group mice, the rearing, horizontal crossing lattice and grooming times decreased, central cell residence time extended, and defecation increased in the model group mice. Compared to model group mice, Chinese herbal compound of Zhijujieyu-tang can improve spontaneous activity and exploratory behavior of depression model mice to adapt new environment, and ease tensions to the new environment. Single herb drug IBO and AGS had a weak effect on improving the open field behavior of mice.2. Tail suspension test: Compared with the control group mice, the immobility time were increased, the latency immobility were decreased significantly in model group mice. Compared to model group mice, the immobility time were reduced and the latency immobility were increased obviously in fluoxetine group and Chinese herbal compound of Zhijujieyu-tang group mice. The degree of despair was eased. The immobility time and the latency immobility in the IBO group and AGS group mice had no significant difference.3. Morris water maze task: Compared with the control group mice, the time of finding the platform in model group mice were significantly prolonged in the place navigation test. In thespatial probe, the residence time of mice in the model group were significantly decreased.Compared to model group mice, the escape latency were significantly reduced in fluoxetine group and Chinese herbal compound of Zhijujieyu-tang group, while the residence time in the platform quadrant was significantly increased. The IBO group and AGS group has not been significantly improved.4. Enzyme activity test: Compared with the control group mice, the CAT activity was decreased and MAO activity was increased significantly in model group mice. Compared to model group, the CAT activity was increased and MAO activity reduced significantly in the fluoxetine group and Chinese herbal compound of Zhijujieyu-tang group. However, IBO group mice and AGS group mice CAT activity and MAO activity had no significant difference.5. HE staining: In the control group, fluoxetine group and Chinese herbal compound of Zhijujieyu-tang group mice, the neurons of CA1, CA3 and DG region is more and less deformation cells. These cells have the same size, complete structure, and the cells are arranged in a neat and compact arrangement. The nucleus locate central of the cell, the structure is obvious and the edge is clear. Nuclear staining is relatively deep. The neurons in PFC are arranged in a regular pattern, and the morphology is regular and the staining is clear.In the model group, AGS group and IBO group mice, the nerve cells of CA1 and CA3 appear atrophy, the number of cells decreased, the gap between the cells became larger, and the cell nucleus was fixed. The nerve cells in PFC are irregular in shape, cell number reduced and loosely arranged, the number of triangular cells and spindle cells appeared, the cells appeared interruption, pale stained and uneven coloring.6. IHC of NCAM: Compared with the control group mice, the number of NCAM positive cells in HP and PFC were decreased significantly in the model group mice, and the average target gray value were increased, the expression of NCAM was weakened significantly.Compared with the model group mice, the number of NCAM positive cells in DG and PFC were increased significantly in the fluoxetine group and Chinese herbal compound of Zhijujieyu-tang group mice, and the average target gray value were decreased. However, the expression of NCAM in CA1 and CA3 was relatively small. The number of NCAM positive cells in the IBO group and AGS group was less.Conclusions are as follows:1. Chinese herbal compound of Zhijujieyu-tang can improve markedly the depression-like behaviors induced by chronic stress in mice, and enhance significantly learning and memory ability of the depression model mice, and that it have a certain antidepressant effect.2. Chinese herbal compound of Zhijujieyu-tang can increase significantly CAT activity and decrease MAO activity, in order to abate neurons injury.3. Chinese herbal compound of Zhijujieyu-tang can increase obviously the expression of NCAM in HP and PFC of the depression model mice. And it can ease and reduces the damage of structural and functional in the HP and PFC.