Based On The Synaptic Plasticity Structure And Functional Protein To Explore The Effect Of Compound Gold Thinking On The Cognition Of SAD Mice

ObjectiveAlzheimer's disease(AD)is a severe and chronic neurodegenerative disease.Because of the occurrence and irreversibility of AD,brought a serious economic and mental burden to society and patients' families.AD is characterized by cognitive dysfunction and brain atrophied,with synaptic and neuronal loss and a large number of(3-amyloid protein deposition as the main neuropathological lesions.In AD neuropathology and morphological studies,it was found that there are obvious synaptic loss in many areas of the cerebral cortex and hippocampus,and the number of synapses in many early patients decreased,and showed changes in synaptic structure and dysfunction.So the synaptic deletion and synaptic plasticity of hippocampal neurons play an important role in the early pathological process of AD and play an important role in the pathogenesis of learning and memory dysfunction of AD.In this study,GAPT(a combination of several active components extracted from the Chinese herbs ginseng,epimedium,polygala and tuber curcumae)was used to intervene in the SAD(sporadic Alzheimer's disease)mouse model for 3 months,and behavioral experiments were used to evaluate the overall animal learning and memory ability.The changes of synaptic protein expression can reflect the changes of synaptic function.In this study,we selected synaptic structure-related proteins drebrin,cofilin,and synaptic function-related proteins synaptophysin,N-methyl-D-aspartate receptor subunit NR2B(NR2B)as observation indicators,observed changes in the expression of synaptic-related proteins,so explored the relationship between GAPT and SAD mice cognitive impairment and the effect of GAPT on synaptic plasticity-related structural and functional proteins.MethodsThe streptozotocin(STZ)was injected into both lateral ventricles of 75 C57/BL6J mice every other day to prepare the SAD model.The model of SAD mice were randomly divided into five groups:model group(0.5%CMC),donepezil group(0.92mg/(kg·d)),GAPT high-dose group(20mg/(kg·d)),GAPT medium-dose group(10mg/(kg·d)),GAPT low-dose group(5mg/(kg d)),with 15 mice in each group,continuous gavage for 3 months.15 C57/BL6J mice were injected with artificial cerebrospinal fluid in both lateral ventricles as a control group(0.5%CMC).At the end of the last gavage,Morris and Step down test were carried out,and the hippocampus of the brain was taken for further detection;The changes of the number of nerve felt and synapses in mice were observed by transmission electron microscopy;The expression of drebrin,cofilin,synaptophysin,NR2B and the number of positive cells were observed by Western blot and immunohistochemical staining.Results1.The effect of Chinese medicine GAPT on learning,memory and spatial retention ability of SAD mice:In the Step down test,the error number of mice in the model group increased significantly compared with the control group(P<0.01),and the error number of mice in the donepezil group,GAPT high-dose group,medium and low dose group decreased to different degrees compared with the model group(P<0.01 or P<0.05).After the sixth day of Morris water maze,the number of crossing platform in the target quadrant was observed.The results showed that the number of crossing platform in the model group was significantly reduced compared with the control group(P<0.01).Compared with the model group,the number of crossing platform in the donepezil group,GAPT high-dose group,medium and low dose group increased in different degrees(P<0.01 or P<0.05).This shows that GAPT can improve the learning and memory ability of SAD mice in different degrees2.The effect of Chinese medicine GAPT on the number of synapses in SAD mice:The number of synapses in the nerve felt was observed under the electron microscope X2K field of view.Compared with the control group,the number of synapses in the hippocampal CA1 area of mice in the model group was significantly decreased(P<0.01);Compared with the model group,the number of synapses in each medicine administration group was more than that in the model group(P<0.01),which reflects the neuroprotective effect of the administration group on synapses from a certain degree.3.The effect of Chinese medicine GAPT on synaptic structure and function related proteins in SAD mice:Western blot and immunohistochemical staining showed that compared with the control group,the protein expression and positive cell distribution of drebrin,synaptophysin and NR2B in the model group were significantly reduced(P<0.01),and the protein expression and positive cell distribution of cofilin were increased(P<0.01);the protein expression and positive cell distribution of drebrin,cofilin,synaptophysin and NR2B in each intervention group were improved in different degrees(P<0.01 or P<0.05),indicating that GAPT may play a neuroprotective role by protecting synaptic structure and function related proteins.ConclusionsGAPT can improve the learning and memory ability of sad model mice induced by STZ bilateral lateral ventricle injection.Its mechanism may be to maintain the plasticity of synaptic structural protein by raise drebrin and reduce cofilin protein,increase the expression of Syn and NR2B protein to promote synaptic transmission,improve synaptic plasticity and protect synaptic function,and provide more theoretical basis for the prevention and development of traditional Chinese medicine in AD.