The Effect Of Flos Albiziae Flavonoids On Learning And Cognitive Ability In MK-801Induced Schizophrenia’s Model Rats And Relative Mechanisms

BackgroundSchizophrenia is a severe mental disease with complex cause and the mechanisms are still not fully investigated. This mental disease can be seen frequently on the young people and accompanied with the disorder of feeling, emotion, behavior, and thinking. The progression of schizophrenia is slow and chronic with a high rate of relapse and morbidity, In recent years, it was found that the flavonoids could protect the central nervous system and improve the physical function and maintain the homeostasis in mental diseases, thus increasing the efficiency of treatment. However, the mechanisms of these effects on the nervous system still need further investigation for developing better understanding on the mechanisms of schizophrenia and for proving more basis of treatment.ObjectiveNon-competitive antagonists of NMD A receptor, dizocilpine maleate (MK-801), was used to establish the schizophrenia’s rat model. The aim of this study is to investigate the effects of Flos Albiziae flavonoids on learning and cognitive ability in schizophrenia’s model rats and to discuss the relative mechanisms through the detection of the changes of relevant proteins such as S100β and c-Fos in the rat model after treatment with Flos Albiziae flavonoids.Methods1. Experimental groups:The rats were divided to4groups which contain10rats in each group. The groups include the control group, model group, HLA-treated group, FAF-treated group. 2. The establishment and treatment of rat model:control and model groups were given physiological saline by intragastric administration,2mg/kg haloperidol was given by intragastric administration in HLA-treated group, and60mg/kg Flos Albiziae flavonoids was administered in FAF group. HLA and FAF groups were treated with drug one time per day for28days. Model, HLA, and FAF groups were injected with0.6mg/kg MK-801one time a day, whereas the control group was injected with physiological saline. After injection with MK-801for3days, Morris water maze test was performed to determine if the model is successful.3. Morris water test:Morris water test was performed in control, model, HLA, and FAF group after the treatment with the drugs and MK-801. The Morris water test imaging system was used to process the result. The learning and cognitive ability of rats in different groups was determined using place navigation test and spatial probe test.4. Detection of expression and location of relevant proteins:After the Morris water test, the rats were administered with4%paraformaldehyde and then the hippocampus was taken out. The location and expression of S100-β, c-Fos were in rat hippocampus detected using immunohistochemical staining, immunofluorescence, and Western blot, respectively.5. Statistical analysis:The SPSS18.0statistical software was used to process the data. Numerical variable data were expressed with (x±s), one-way ANOVA were used to compare these data. p<0.05was regarded as statistically significant.Results1. Measurement of escape latent period:The rats in the control group had the most short escape latent period, indicating the highest learning ability. The escape latent period of the rats in the model, HLA, and FAF group was extended compared to the rats in the control group. The escape latent period of the rats in HLA and FAF group was significantly decreased compared to that in the model group (p<0.05and p<0.01, respectively). However, the escape latent period of the rats between HLA and FAF group has no difference (p>0.05).2. Detection of spatial memory:The rats in the control group cross the platform for the most times, showing the highest ability of memory. The rats in the model, HLA, and FAF group showed lower times to cross the platform compared to the rats in the control group. The time to cross the platform in HLA and FAF group was significantly increased compared to model group (p<0.01). The time between rats in HLA and FAF group has no significant difference (p>0.05).3. Immunohistochemical staining:Few S100β or c-Fos positive cells were observed in the control group. In model group, the expression of S100β or c-Fos was increased compared to that in control group. Rats in HLA and FAF group expressed lower level of S100β or c-Fos compared to that in model group (p<0.01). The expression of S100β or c-Fos has no change between HLA and FAF group (p>0.05).4. Immunofluorescence:S100β or c-Fos positive cells in the control group was lower than that in the model group (p<0.01). Green fluorescent cells were observed in rats in HLA and FAF group. However, the number of fluorescent cells in these two groups is smaller than that in model group (p<0.01). No difference in the number of positive cells was observed between HLA and FAF group (p>0.05).5. Western blots:S100β and c-Fos were expressed in lower level in hippocampus control group. The expression of these two proteins was significantly increased in model group (p<0.01). However, the expression of S100β and c-Fos in HLA and FAF group was significantly reduced compared to that in the model group (p<0.01). Hippocampus cells in HLA and FAF group expressed similar level of S100β and c-Fos (p>0.05).Conclusion1. Flos Albiziae flavonoids could protect the neuron system and improve the learning and cognitive ability of schizophrenia’s model rats;2. Flos Albiziae flavonoids reduce the expression of S100β and c-fos in model rats’ hippocampus cells, thus leading to the protection of theneuron system.