Study About The Brain Protective Effect And Its Mechanism Of CPPS On Cycloheximide Induced Memory Consolidation Disorder In Mice

In the aging of society,physiological or pathological aging problem is increasingly serious.The study and the treatment of learning and memory,which is closely related to neurodegenerative diseases such as natural aging,and AD or VD,have important medical and sociological significance.The process of learning and memory requires the mutual transformation of short-term memory and long-term memory.The external information obtained by the brain is strengthened and integrated,and becomes stable after being stored in specific brain regions.And learning and memory is regulated by neurotransmitters and neurohormones in the brain.Protein synthesis during transformation is essential for memory consolidation.c AMP response element binding protein（CREB）is an important nuclear transcription factor,which is the intersection of many intracellular signal transduction pathways.And CREB affects the regeneration of neurons,the generation of synapses and the development of learning and memory.In addition,increased intracellular Ca²⁺levels lead to phosphory-lation of CREB,which adjust the formation of new synaptic connections and the formation of long-term memories.Ca²⁺binds to Ca²⁺binding protein（Ca M）,and then activate the calmodulin dependent protein kinase（CaMK）.CaMKⅡand CaMKⅣare important protein kinases of CREB.So further research on through regulation of intracellular Ca²⁺levels,then influence of Ca²⁺/CaMK/CREB pathway,which will help us to investigate how to improve learning and memory.Plant polysaccharides have good effects and low toxicity.They have been received widespread attention and have become one of the new directions in the development of new drugs,food and health care products.Studies have shown that many plant polysaccharides,such as lycium barbarum polysaccharides,astragalus polysaccharides and codonopsis pilosula polysaccharides,can play a protective role in the brain.Through different mechanisms,such as immune enhancement,anti-inflammation and anti-oxidation,they play a protective role in the brain.Codonopsis pilosula polys polysaccharide（CPPS）is one of the most important active components in radix Codonopsis.It can not only fight aging and enhance immunity,but also fight coagulation and inhibit oxygen free radicals.In addition,studies have shown that CPPS can improve the learning and memory impairment caused by scopolamine and sodium nitrite in mice.And CPPS has an anti-aging effect on D-galactose-induced aging model mice.However,whether CPPS can improve the memory consolidation disorder caused by cycloheximide and the detailed mechanisms of brain protective have not been reported.In this study,cycloheximide,a protease inhibitor,was used to promote spatial memory consolidation in mice.We try to investigate the protective effect of CPPS on learning and memory and its possible mechanism.The mice were divided into normal control group,model group,positive control group,CPPS 300mg·kg^-1 group,and CPPS 150mg·kg^-1 group.Mice in each group were given the drug by gavage for 15 consecutive days.Then the spatial memory and spatial exploration experiments of Morris water maze were carried out,and the changes of the learning and memory console-dation ability of each group were observed for 5 consecutive days.During this period,cycloheximide(120mg·kg^-1)was intraperitoneally injected to inhibit the synthesis of memory proteins,resulting in memory console-dation disorders.After the end of the behavioral experiment,the brain was taken from the severed head,the hippocampal tissue was stripped off,and the protein was extracted.The contents of specific proteins PKA,CaMK and CREB in the hippocampal tissue of mice were determined by ELISA.And western blot method is used to detect the protein expression of CaMKⅡand CREB of hippocampal tissues in mice.Then we try to clarify the mechanism of action of CPPS to improve memory consolidation disorder from the molecular level.The results of Morris water maze experiment showed that intra-musitoneal injection of cycloheximide could cause memory consolidation disorder in mice（P<0.01）,and piracetam(500mg·kg^-1),CPPS 300mg·kg^-1and CPPS 150mg·kg^-1 could improve spatial memory disorder and spatial exploration ability of mice in different degrees（P<0.05,P<0.01）.ELISA results showed that compared with the normal control group,there were significant differences in PKA,CaMK and CREB contents in the hippo-campal tissues of the model group（P<0.05,P<0.01）.Compared with the model group,the contents of CaMK and CREB in the hippocampal tissues of mice in the piracetam group and the different doses of CPPS increased significantly（P<0.05,P<0.01）.Western blot results show that compared with normal control group,the CaMKⅡand CREB protein expression of hippocampus had significant difference in model group mice（P<0.05,P<0.01）;Compared with model group,CaMKⅡand CREB protein expression of hippocampus were significantly increased of piracetam group and each dose CPPS groups mice（P<0.05,P<0.01）.The results show that the cyclohexanol imide can cause memory consolidation disorders in mice,and related to its influence CaMK/CREB signaling pathways.CPPS can improve the memory consolidate obstacle induced by cyclohexanol imide,which related to raise the protein expression of CaMKⅡ/CREB signaling pathway.