Effect Of β Sheet Breaker On CRTC1-BDNF Signal Pathway On Double Transgenic AD Mice

Objective: To explore the effects of β-sheet blocking peptide drugs HPYD and H102 on the related proteins in the hippocampal CRTC1-BDNF signaling pathway of APP/PS1 double-gene AD model mice,and to explore HPYD and H102-BD can improve the learning and memory function of AD mice through the influence of CRTC1-BDNF signaling pathway.Method: 52 8-week-old APP/PS1 double transgenic male AD model mice were randomly divided into model group,HPYD administration group,H102-BD administration group,and donepezil administration group(positive drug control group),13 rats in each group.13 C57BL/6J male mice of the same age as the background were used as a control group.The mice in HPYD and H102-BD administration groups were separately given 5μl of HPYD and H102-BD solution(5.8 mg/kg)daily.The mice in the control group and the model group were given the same amount of blank adjuvant solution daily.The donepezil group was given water.Medicine.Six weeks after the administration,a new object recognition experiment was used to test the learning and memory ability of each group of mice.Six weeks after the administration,a new object recognition experiment was used to test the learning and memory ability of each group of mice.At the end of the behavioral experiment,the mice were killed.The mice were intraperitoneally injected with 10% chloral hydrate anesthesia,followed by PBS perfusion,decapitation on the ice,the brain tissue of one side of the mouse was isolated from the hippocampus and frozen at-80 ° C,then used for qPCR,Western blot Experiment.The transcription level of APP,CRTC1 and BDNF gene in APP/PS1 double transgenic mice was identified by real-time fluorescent quantitative PCR.The expression levels of CRTC1,BDNF and Trk B protein in hippocampus of each group were determined by Western blot.Result:(1)New object recognition experiment: Compared with the control group,the recognition index of new objects in the model group was lower(P<0.05).Compared with the model group,the new object recognition index of HPYD group,H102-BD group and donepezil group increased(P<0.05);there was no statistically difference between the HPYD group,the H102-BD group and the donepezil group(P>0.05).(2)qPCR results: Compared with Control mice,the expression of APP m RNA in hippocampus of APP/PS1 double transgenic AD mice increased(P<0.05);compared with Control group mice,the expression level of CRTC1 and BDNF m RNA in hippocampus of APP/PS1 double transgenic AD mice decreased(P<0.05).(3)Western blot results: Compared with the Control group,the expression of BDNF protein in hippocampus of AD group decreased,the difference was statistically significant(P<0.05);Compared with AD group,the expression level of BDNF protein in hippocampus of HPYD,H102-BD and Donepezil group increased,the differences were statistically significant(P<0.05);there was no statistical difference in the expression of BDNF in hippocampus among HPYD,H102-BD and Donepezil(P>0.05).There was no statistical difference in the expression of CRTC1 protein between Control and AD group(P>0.05);compared with AD group,the expression of CRTC1 protein in hippocampus of HPYD,H102-BD and Donepezil group increased,the difference was statistically significant(P<0.05),there was no statistical difference in the expression of CRTC1 in hippocampus among the three groups of HPYD,H102-BD and Donepezil(P>0.05).Conclusion: The β-sheet blocking peptide drugs HPYD and H102-BD may improve the learning and memory function of AD mice.HPYD and H102-BD may improve the expression level of CRTC1-BDNF signaling pathway-related protein in hippocampus of AD mice.