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Effect Of Electroacupuncture On Aβ And LRP1 Levels In Hippocampus Of APP / PS1 Double Transgenic

Posted on:2016-05-15Degree:MasterType:Thesis
Country:ChinaCandidate:F LiFull Text:PDF
GTID:2134330461493044Subject:Acupuncture and Massage
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Beta-Amyloid (A β)cascade theory is the most recognized pathogenesis of Alzheimer’s disease (AD).The clearance of A β in blood brain barrier is very crucial for A β level in late-onset AD brain. As the major transporter clearing A β though blood brain barrier,low-density lipoprotein receptor-related protein-1 (LRP1),which is on the cerebral microvascular endothelial cell membrane can bind directly or indirectly with A β,which actively transports A β from brain to blood. When LRP1 level decreasing,A β in the brain is accumulating, which accelerating the pathological procession of AD. The APP/PS1 double transgenic mouse is one of the commonly used AD models. It is shown that senile plaques(SP) and LRP1mRNA reduction in 5-month-old APP/PS1 transgenic mice’s brain tissue.The disturbance of A β clearance in the brain will lead to change cerebral blood flowing and cerebral microvascular amyloid deposition.Elderly people with AD prone to have kidney deficiency, blood stasis and toxin, blocking collaterals that causing AD.as the traditional Chinese medicine theories says.Refreshing mind, tonifying kidney.dispelling poison,and dredging cerebral collateral,would be the principle and method of the acupuncture treatment for AD.Whether acupuncture can dredge cerebral collateral or not?Our study pay more attention on the A β Clearing through BBB removal approach angle,which finding that electro-acupuncture (EA) leading the transport receptor low-density-lipoprotein-receptor-1 related protein (LRP1) level more higher,while A β level becoming lower.Therefore, our study took EA at Baihui (DU20), Yongquan (K1) for six weeks, using APP/PS1 transgenic mice as animal models of AD.Morris water maze oed to test APP/PS1 transgenic mice learning and memory behavior changes. A β1-40.A β1-42, A β1-42/40 in the hippocampus were measured by ELISA. LRP1 protein level in the hippocampus were measured by Western blot.LRP1mRNA level were measured by real-time PCR.The present experiment will explain acupuncture maybe can effect the A β clearance pathways transporter LRP1 and LRP1mRNA in blood brain barrier, and to provide experimental basis for the mechanism of the influence of EA on AD.ObjectiveTaking EA at Baihui (DU20), Yongquan (K1) on six weeks of APP/PS1 transgenic mice as animal models of AD for 6 weeks,to find out the effect of acupuncture on the level of β -amyloid (A β) and its key transporter LRP1 and LRP1mRNA in APP/PS1 transgenic mice, to explore whether electro-acupuncture reducing A β level by LRP1mRNA and LRP1 or not.Methods4-month-old APP/PS1 transgenic mice were randomly divided into model group (M), EA group (EA).Non-transgenic litter-mate mice were used as control (C). Mice in EA group were given acupunctured Yongquan, Baihui 0.1mA,15min,1 time every other day, for 6 week. The 2nd-5th day after treated,they all had taken Morris water maze test. Collected hippocampus specimens the 7th day after treated. A β 1-40,A β1-42,and A β1-42/40 in the hippocampus were detected by ELISA.Western blot was used to detect LRP1.Real-time PCR was used to detect LRP1mRNA expression in hippocampus.Results1. The Morris water maze test showed the escape latency,the number of platform-site crossover,the time spent in platform quadrant,which we put the mice in the fourth quadrant in each group were not significant different(P>0.05).2.The A β 1-42, A β 1-40,and the A β 1-42/A p 1-40 levels of the model group were all higher than that of normal control group and acupuncture treatment group(P<0.01).3. In model group, LRP1 and LRP1mRNA relative expression quantity were lower than that in the normal control group (P<0.05).Compared with model group, LRP1 and LRP1mRNA in the EA group had an upward trend, but there were no significant difference (P>0.05).ConclusionEA may decrease the level of A β1-40, Aβ1-42 and the ratio of A β 1-40/A β 1-42 in their hippocampus.
Keywords/Search Tags:Alzheimer’s disease(AD), βamyloid protein(A β), APP/PS1 double transgenic mice, Electro-Acupuncture(EA), low density lipoprotein receptor-related protein-1 (LRP1)
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