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Effect On Electro-acupuncture "Baihui" And "Yongquan" Intervention On Aβ Stain And Blood Brain Barrier Clearance On The Hippocampus In Of APP/PS1 Double Transgenic Rats

Posted on:2016-12-27Degree:DoctorType:Dissertation
Country:ChinaCandidate:W L A B L Z JiaFull Text:PDF
GTID:1224330461993023Subject:Acupuncture and Massage
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1 ObjectiveAlzheimer’s disease (AD) is a neurodegenerative disease and the most common type of dementia in the elderly. The symptoms are memory impairment, decreased learning ability, language dysfunction, spatial perception disorder, a decline in computing power, theosophy apathy, depression, paranoia and more. AD causes serious damage to the viability of a patient and also affects their social functionality. Patients’families also face dealing with an emotionally and physically draining burden-one of the most serious issues faced in today’s aging society. Taking into account many previous studies of AD pathogenesis, the most prevalent and recognized hypothesis is the A(3 toxicity hypothesis; this is the hypothesis which is studied the most.which cascades theory amyloid peptide is recognized as the highest degree a hypothesis, It emphasizes that the accumulation of Aβ leads to the formation of SP, which in turn causes synapse reduction, nerve dysfunction and neuronal death. The clinical symptoms of dementia play a key role in the formation of neurotoxic fibers, and thus the composition of the pathological features of Alzheimer’s disease-age spots. Therefore, inhibiting the secretion of Aβ and clearing pathways of the protein is, today, the main practice for the treatment of AD.2 Research MethodsIn this study, experimental methods preclude the use of animals-APP/PS1 double transgenic mice and APP/PS1 double transgenic negative mice-as research subjects. The APP/PS1 double transgenic mice are divided into a model group, EA group and drug group. The APP/PS1 double transgenic negative mice act as the control group. The mice are treated every other day over a period of five weeks, after which the Morris water maze test is used to detect and evaluate behavior changes in the four groups of mice and to compare what effects acupuncture treatment and drug treatment have on learning and memory functions.Immunohistochemistry expression observed four groups of mice brain hippocampus Aβ1-42 and LRP1 compared acupuncture treatment with the drug effects on Aβ generation and treatment through the blood brain barrier to clear pathways;Using western blotting to observe the relative expression of LRP1 in APP/PS1 transgenic mice hippocampus; Using transmission electron microscopy to observe the four groups of mice brain synapses in the hippocampus, age spots, nerve cells, microvascular ultrastructure of hippocampus influence the situation, comparing acupuncture therapy and drug therapy ultrastructure of the hippocampus and hippocampal senile plaques ultrastructure of deposition;3 Results3.1 The results of the Morris water maze test were as follows; compared with the model group, the electro-acupuncture group and the control groups’ escape latency was significantly shorter, P<0.05, a significant difference;Compared with the EA group, the model group and the drug groups’escape latency was significantly prolonged.P<0.05, with significant differences; After four days of training each group of mice experienced decreased escape latency, all four groups of mice had measurable and significant differences when comparing the first to the fourth day. The escape latency of the overall model mice showed a "Platform-Platform-down" trend. The escape latency of the EA group as a whole was "Platform-down-Platform". The escape latency of the drug group as a whole was "Platform-Platform-down". The escape latency of the overall control mice showed a "down-down-down" trend. In terms of the total swimming distance; after four days of training, each group of mice experienced a decrease in the total distance swam; The model group’s swimming distance overall followed the "platform-down-down" trend. The EA group’s swimming overall followed the "up-down-up" trend. The drug group’s swimming overall followed the "platform-down-down" trend. The control group had a significantly shorter total swimming distance and overall followed the "down-down-down" trend.2) The space exploration experiment in the target quadrant showed no significant difference in time and total distance swam.3) Immunohistochemistry expression shows that the model group rats showed a significantly higher level of AP 1-42 than the control group and a significantly lower level of LRP1. Study of the EA group showed reduced levels of Aβ 1-42 and higher levels of LRP1 compared with the model group.4) LRP1 Western blotting result shows that compared with the control group, the model group mice hippocampus LRP1 expression was significantly reduced; compared with the model group, EA group the relative expression of LRPlin hippocampus was significantly increased; the drug group the relative expression of LRP1 significantly increased; compared with the acupuncture group, the relative expression of LRP1 in hippocampus of mice in drug group had no significant difference;5) The TEM results indicate that:the model groups’ hippocampus developed SP. The hippocampal ultrastructure displayed Alzheimer’s disease-like changes.The EA group also developed hippocampal SP. The ultrastructure of the EA group’s hippocampus was significantly better than that of the model group.4 Conclusions4.1 EA treating "Baihui" "Yongquan"-the treatment of 10-month-old APP/PS1 double transgenic mice could result in a significant improvement in learning ability, do not have significantly influence on space exploration ability.4.2 Donepezil hydrochloride to treat APP/PS1 double transgenic mice-may not improve their learning ability and space exploration ability;4.3 EA to treat "Baihui" "Yongquan"-10-month-old APP/PS1 double transgenic mice may be able to activate nerve cells autophagy system and effectively remove intracellular Aβ precipitate4.4 Donepezil hydrochloride treatment may reduce the Aβ deposition in 10-month-old APP/PS1 hippocampus, did not increase the cell surface receptors LRP1 expression in hippocampus, it may reduce the content of deposition of Aβ in the brain through another pathway;...
Keywords/Search Tags:Alzheimer’ sdisease, APP/PS1, , Blood brain barrier, Hippocampus Ultrastructure, LRP1, Synapse
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