The Effect Of Electroacupuncture On The Levels Of BACE-1, ?-CTF, ?-secretase And A?1-42 In Frontal Lobe Of APP/PS1 Transgenic Mice At 4 Months Of Age

The pathogenesis of AD is very complicated.At present,there are many hypotheses about the pathogenesis of AD.Among the many hypotheses,the A? cascading hypothesis is a public pathology mechanism that is more acceptable to the public.The hypothesis is that in the early stage of the disease,the abnormal cleavage of amyloid precursor protein APP and the clearance function of A?in the brain are reduced,and the dynamic balance between the generation and clearance of A? in the brain is broken,leading to the overall level of A(3and the ratio between type A?1-42 and A?1-40 increases.Excessive amounts of A?in the brain,particularly A(31-42,can be converted into highly toxic oligomers in a short period of time.This oligomer can cause abnormal synaptic function in the nervous system.During the progression of the disease,A? gradually forms a dispersed substance in the form of oligomers,and eventually forms amyloid plaques that accumulate in the brain.It is particularly important that ?-secretase and y-secretase cleave APP proteins at corresponding sites to generate A?.In the amyloid-like hydrolysis pathway,APP is first cleaved by ?-secretase,which acts as a protease with full function of ?-secretase and interacts with APP to produce soluble APPN-terminal fragment sAPP?and The APP C-terminal fragment which contains 89 or 99 amino acid residues,also known as ?-CTF.?-CTF will produces A? 1-42 by the?-secretase acting between alanine Ala713 and threonine Thr714..Clinical reports show that acupuncture orCombination of acupuncture and medicine to treat with AD has a significant clinical effect,AD patients have improved cognitive function and living ability.those indicats that acupuncture can reduce A?levels in the brain of AD patients,and this effect may be achieved by affecting the process of cleavage from APP to A?production.Therefore,this experiment aims to investigate the APP amyloid liked Cracking process that can generate A(3.If changes in BACE-1,?-CTF,and ?-secretase levels occur during the intervention,it may be suggested that acupuncture may have an effect on the process of APP to A? thereby reducing A? levels in the brain.ObjectiveUsing APP/PS1 transgenic mice as an animal model,electroacupuncture stimulate"Baihui and Yongquan" acupoints to observe whether electroacupuncture can decrease the level of A?in the brain by effecting the level of BACE-1,?-CTF and ?-secretase in the APP amyloid liked Cracking process.Methods4-month-old male APP/PS1 transgenic mice(n=14)were randomly divided into an electroacupuncture group and a model group,7 in each group.7 male C57BL/6 wild type mice were Applied as the normal control group.Electroacupuncture group acupuncture Baihui and bilateral Yongquan points,horizontal insertion 2?3mm,bilateral Yongquan points ues the electro-acupuncture instrument,density wave,frequency 1/50Hz,intensity 0.1mA,by seeing the needle handle Slight flutter,Treated every other day,15 mins each time,totally last 2 weeks.The model group and the normal control group were tied with a mice bag for 15 minutes in the same manner every other day.Total intervention for 2 weeks.After the intervention treatment,6 sets of frontal lobes were taken from each group of mice and Elisa technique was used to detect the level of?-secretase BACE-1,?-CTF,y-secretase and its final production A?1-42of 4 months old APP/PS1 transgenic mice,to determine whether the electro-acupuncture have effects on the process.ResultsThe level of A?1-42 in the frontal lobe of the model group was higher than that of the normal group,there are Statistically significant differences(P<0.01),and the level of A?1-42 in the frontal lobe of the electroacupuncture group was lower than that of the model group(P<0.01).The level of A?1-42 in the frontal lobe of APP/PS1 mice was indeed higher than that of normal mice,and the level of A?1-42 was decreased after electroacupuncturetreatment.The BACE-1 level in the model group was higher than that in the normal group,here are Statistically significant differences(P<0.01),while the BACE-1 level in the electroacupuncture group was lower than that in the model group(P<0.01).The expression level of BACE-1 in the frontal lobe of APP/PS1 mice was higher than that in normal mice,but the level of BACE-1 was decreased after electroacupuncture treatment.The level of ?-CTF in the model group was higher than that in the normal group,here are Statistically significant differences(P<0.01),and the level of ?-CTF in the electroacupuncture group was lower than that in the model group(P<0.01).It was suggested that the production of ?-CTF in the frontal lobe of APP/PS1 mice increased,but the production of ?-CTF decreased after electroacupuncturetreatment.There was no significant difference in the level of ?-secretase between the frontal lobes of the three groups of mice(P>0.05)This may indicate that the level of ?-secretase in the frontal lobe of 4 month-old APP/PS1 mouse model was not different from that in wild-type mice,and the increase in A? 1-42 level was caused by the increase in BACE-1 cleavage APP.the intervention of electroacupuncture on the APP amyloid lysis pathway only acts on BACE-1,whereas the y-secretase only acts on the reduced ?-CTFnormally.ConclusionElectroacupuncture intervention can reduce the level of A?1-42 in the brain of AD mice,and this effect may reduce the reduction of A? production by affecting the cleavage of APP precursor protein by ?-secretase BACE-1.