Based On The Regulatory Mechanism Of Synaptic Plasticity Jiawei Sini Decoction On Sleep Deprivation In Rats Learning And Memory Impairment

Learning and memory is the highest function of the brain——an important component of intelligence. To Individual, learning refers to the process of acquisition of new knowledge. Memory is on access to knowledge encoding, consolidation, retrieval. In advanced animals and humans, learning and memory are the most important kind of method in order to adapt to the environment. Sleep is closely related to learning and memory.ln this subject, the researcher would observe the changes of the ability of learning and memory of sleep deprived rats and the effect of three Chinese formulas.PartⅠthe Theoretical StudyBy literature study, the relation of Chinese Five Viscera containing God.and learning and memory was discussed.The narrow god of Chinese medicine can be divided into five directional gods and Emotions. The God of Chinese Five Viscera influence each other, and regulate the process of learning and memory. Sleep-wake cycle is controlled by the God of Chinese Five Viscera.Sleep deprivation can damage the function of the God of Chinese Five Viscera.PartⅡExperimental StudiesIn this part, we focus on the researches of mechanism of molecular biology of learning and memory capacity changes caused by Sleep deprivation. The learning and memory capacity through establishing animal models of Sleep deprivation was evaluated. Using western blot and fluorescence quantitative PCR methods, the changes of protein and gene xpression of NMDA and EphB2 receptors in different brain regions of model rats were observed. The changes of the ultrastructure of rat prefrontal cortex and hippocampus were observed using transmission electron microscopy. Different Chinese herbs were used to intervene for animal models, and their roles in medicine mechanisms were investigated. Main content and the results are as follows:Experiment One:Evaluation of the Abilities of Learning and Memory of Sleep Deprived Rats.Objective:To observe the changes of the ability of learning and memory of sleep deprived rats and the effect of three Chinese formulas.Methods:Changes of learning and memory capacity were observed using Y maze.Results:Compared with the control group, the Y maze correct percentage in the model group obviously decreased (P<0.05). Compared with the model group, the Jiawei Sini Powder group can obviously increase the Y maze correct response rate(P<0.05).Conclusion:Jiawei Sini Powder could improve sleep deprived rats'ability of learning and memory.Experiment Two:Study of Effect of Jiawei Sini Powder on the Changes of behaviour of Sleep Deprived Rats.Objective:To investigate the behavioral changes of 168h of sleep deprived rats and the effect of three Chinese formulas(Sini Powder, Shenghui Decoction and Jiawei Sini Powder).Methods:The rats were deprived sleep for 168 hours using multi-platform method. Experimental rats were randomly divided into the control group, the model group, the Sini Powder group, the Shenghui Decoction group and the Jiawei Sini Powder group, fifteen in each.Corresponding medicines and distilled water were given to them every day.The intervention groups were fed with Sini Powder,Shenghui Decoction and jiawei Sini Powder, and the dosages are 2.5g/kg-1,13.75g/kg-1,16.25g·kg-1.To observe the behavioral changes of rats using open field and elevated plus-maze test.Results:After 168h of sleep deprivation, rats made significantly more entries into the open arms and inner zone than control group in the elevated plus maze and standard open field tests. Rats of Jiawei Sini Powder group spent significantly less time in the open arms and inner zone than sleep deprivation group.Conclusion:The study indicates Jiawei Sini Powder can significantly influence abnormal changes of anxiety-like behavior and explore behavior of sleep deprived rats.Experiment Three:Experimental Study of Effect of Jiawei Sini Powder on the Changes of Synaptic Plasticity in PFC and hippocampus in Sleep Deprived Rats.Objective:To observe the effect of jiawei Sini Powder on learning and memory and the changes of synaptic plasticity in PFC and hippocampal CA3 subfield in sleep deprived rats. Methods:The changes of the ultrastructure of rat prefrontal cortex was observed using transmission electron microscopy.Results:Compared with control group, the percentage of correct responses of model group was significantly decreased (P<0.05).The percentage of correct responses of Jiawei Sini Powder group was significantly higher than model group (P<0.05).Compared with control group, in PFC and hippocampal CA3 area of the model group,the thickness of PSD was significantly declined (P<0.05) and Synaptic cleft was significantly widened (P<0.05).Compared with model group, in hippocampal CA3 area of the Jiawei Sini Powder group,the thickness of PSD was significantly added (P<0.05) and Synaptic cleft was narrowed (P<0.05).Compared with model group, in PFC area of the Jiawei Sini Powder group,the thickness of PSD was significantly added (P<0.05)). Compared with model group, in hippocampal CA3 area of the Sini Powder group and Shenghui Decoction group,Synaptic cleft was significantly narrowed (P<0.05).Conclusion:By influencing synaptic Structural plasticity in PFC and hippocampal CA3 area, Jiawei Sini Powder can improve the ability of learning and memory in sleep deprived rats.Experiment Four:Effect of Jiawei Sini Powder on ProteinExpressions of PFC and Hippocampal CA3 area NMDA and EphB2 Receptor in Sleep Deprived RatsObjective:To study protein expressions of PFC and hippocampal CA3 area NMDA and EphB2 receptor in sleep deprived rats, and observe effects of Sini Powder, Shenghui Decoction, and Jiawei Sini Powder on them. Methods:Protein expressions of NR2A, NR2B, NR2B(Tyr1472) and EphB2 receptor in sleep deprived rats were quantitatively analyzed using Western blot technology.Results: Compared with the control group, protein expressions of NR2A, NR2B, NR2B(Tyr1472) and EphB2 receptor in PFC area obviously decreased (P< 0.05),and protein expressions of NR2B in hippocampal CA3 area aslo decreased(P <0.05). Compared with the model group, Jiawei Sini Powder group could obviously improve protein expressions of NR2A, NR2B, NR2B(Tyr1472) and EphB2 receptor in PFC area (P<0.05), and increase protein expressions of NR2B, in hippocampal CA3 area (P<0.05). Compared with the model group, both Sini Powder group and Shenghui Decoction group could obviously improve protein expressions of EphB2 receptor in PFC area (P<0.05).Conclusion:Sleep deprivation could reduce protein expressions of NR2B, NR2B(Tyr1472)and EphB2 receptor in PFC area, and decrease protein expressions of NR2B in hippocampal CA1 area. Jiawei Sini Powder could improve rats'ability of learning and memory, which might be possibly achieved through up-regulating protein expression of EphB2 and NR2B receptor, and changing the synaptic plasticity of hippocampus and PFC.Experiment Five:Effect of Jiawei Sini Powder on mRNAExpressions of Hippocampal CA1 area NMDA Subunit NR2A and NR2B, and EphB2 Receptor in Sleep Deprived RatsObjective:To study mRNA expressions of hippocampal N-methyl D-aspartate (NMDA)receptor subunit NR2A and NR2B, and EphB2 receptor in sleep deprived rats, and observe effects of Sini Powder, Shenghui Decoction, and Jiawei Sini Powder on them. Methods:Gene expressions of NMDA subunit NR2A and NR2B, and EphB2 receptor in sleep deprived rats were quantitatively analyzed using fluorescence quantitative PCR.Results:Compared with the control group,mRNA expressions of NR2B and EphB2 receptor in hippocampal CA1 area obviously decreased (P<0.01), with no obvious change of NR2A Compared with the model group, Jiawei Sini Powder group could obviously improve mRNA expressions of NR2A, NR2B and EphB2 receptor(P<0.01).No statistical difference was found between the Sini Powder group and the Shenghui Decoction group.In hippocampal CA1 area,mRNA expression of NR2A could be more obviously increased in the Shenghui Decoction group than in the model group (P<0.01).Conclusion:Sleep deprivation could reduce gene expressions of NR2B and EphB2 receptor in hippocampal CA1 area. Jiawei Sini Powder could improve rats' ability of learning and memory, which might be possibly achieved through up-regulating mRNA expression of EphB2 and NR2B receptor in hippocampal CA1 area, and changing the synaptic plasticity of hippocampus.SummaryJiawei Sini Powder could improve rats' ability of learning and memory, which might be possibly achieved through changing the synaptic plasticity of PFC and hippocampus. Smoothing Liver Qi and replenishing Kidney play an important role in the process of regulating learning and memory, but can't independently operate this process. When nourishing Heart, smoothing Liver Qi and replenishing Kidney were taken together, the ability of learning and memory would be improved.