| Objective: Alzheimer's disease(AD) is a disease mainlydemonstrateted the symptoms of cognitive handicap of progressivehypomnesia occurred at the presensium or senectitude,which accompanied by psychological and dystropic neurodegene-rativesymptoms. Its characteristic clinical manifestations isa serious decline in learning and memory function, analyticaljudgement capacity of a recession, emotional changes, behavioraldisorders, and even clouding of consciousness, which hasseriously affected the daily lives and social activities ofolder people and led to a decline in the quality of their life.The world's aging population is accelerating. The fifthcensus shows that our country has already become an agingcountry. Till the middle of this century, old people over 60years old will reach about 4 billion, in other words, there willbe one old people in every 4 at that time. As a result, eachcountry including ours has accelerated the research work ofAD's prevention and treatment. Therefore, the keystone andbreakthrough of AD's research consists in the effectiveimprovement of AD patients' learning-memory ability and theirlife quality. The pathogenesis of AD is complicated. Many signalingmolecules have played an important role in it and some signalingpathways have taken part in the process. However, thesingle-gene or single-target therapeutic drugs for AD onclinical are not able to improve or control the patients'symptoms effectively, and also the therapeutic effect islimited and has obvious side effects. To deal with the disad-vantageof the single-target drugs towards the complex diseases,in these years, scientific researchers have presented and triedbringing multi-target treatment strategy into application ofAD's therapy. The reason is that the complex diseases happeninghas usually involved various signaling pathways, while theeffect of single-target drugs have always ignored thebiological macromolecules' interactions in cells and networksystem's interconnections formed in the signaling pathways.And the researcher has indicated that protecting membrane andvarious signal transduction pathways from Aβand others'injury may be the breakthrough of promoting AD patients'cognitive function and AD's prevention and treat-ment.Acupuncture gets widespread concern in the medicalprofession due to its exact effect, permanent effect and no sideeffects. In recent years, acupuncture therapy has got a greatimprovement in the clinical and experimental research of AD'sprevention and treatment. Comparison shows that acupuncture'stherapeutic effect is no worse than Chinese and westernmedicines, or even trend to be better than western medicinesin some part. At the same time, acupuncture therapy with itstherapeutic advantage of multi-target, multi-avenue and multi-levelhas also accorded with the multi-target therapeutic stra- tegy of modern medicine to the complex diseases. Therefore,making the deep research of acupuncture's intervention effectto AD will make great senses to get further understanding ofaging and acupuncture's mechanisms and consequently enhancethe clinical research.Therefore the experiment starts with the related centralsignal transduction of learning-memory to make the furtherexplore on the central mechanism of AD's acupuncture treatment,which provides the experimental evidence for AD's clinicaltreatment.Methods: SD rats were randomly divided into 4 groups: thenormal group, sham-operated group, model group, EA group.Bilateral hippocampus were injected condensed Aβ25-35 to beprepared for rat model of AD. Electro-acupuncture group wereselected bilateral "Shenshu" points, bilateral "Neiguan"points and "Dazhui" points, then connected G6805-Ⅱtype ofelectroacupuncture therapeutic apparatus. We selected thefrequence of 2Hz continuous wave and the intensity of 1mA, last20min, every day one times, 6 times a week, a total of two weekstreatment. We used Morris water maze to test the changes inlearning and memory abilities in each group; used HE stainingto observe the group of morphological changes in rat hippo-campusby light microscope; used spectrophotometric method todetect the changes of Glu in each group; used radioimmunoassayto detect the hippocampal cAMP in each group changes; usedimmunohistochemistry to detect the expression changes of PKAand CREB protein in hippocampus in each group;and usedhybridization in situ to detect NMDAR1mRNA changes in hippo-campusin each group. And make a further analysis on the effect of electro-acupuncture's intervention to every index above.Results:①Compared with the normal group, there was nosignificancein sham operation group in positioning navigationexperiment(P＞0.05); compared with the sham operation group,the escape latency of rats in model group rats was longer thanthe former, there was a significant difference(P＜0.01);Compared with model group, EA group learning and memory in ratssignificantly increased(P＜0.05).②In space exploration experiments,there was no significance(P＞0.05) between sham-operatedgroup and normal group; compared with the sham operationgroup, the reduction of the number across the platform in modelgroup of rats was a significant difference(P＜0.01); Comparedwith model group, the memory of rats in electroacupuncturegroup has improved, there was significance(P＜0.05).③HEstaining: the neurons staining were clear, round, oval orconical, neatly arranged closely in normal group and shamoperation group rat hippocampal. Nuclear circular, large andclear, nucleolus obvious morphological integrity. In modelgroup, the number of rat hippocampal neurons decreasedsignificantly;the loss phenomenon were apparently, residualnerve cells arranged loosely and irregularly; the majority ofcell nuclei pyknosis, nucleolus unclear, Nissl body reduced ordisappeared, the whole deeply stained cells red, CAl area andCA3 area were markedly. Electro-acupuncture can obviouslyimprove the above-mentioned neuronal damage, so that increasethe number of hippocampal neurons, with a more tidy karyopy-knosisphenomenon improvement.④The testing result of spectropho-tometricshowed: Glu of model group's hippocampus weresignificantly higher than the sham group, and there was a significant difference (P＜0.01); Compared with model group,Glu of EA group's hippocampus decreased significantly(P＜0.05)⑤The testing result of radioimmunoassay showed: Compared withsham-operated group, cAMP content of model group's hippocampusdecreased significantly(P＜0.01); Compared with the modelgroup,the cAMP content of EA group's hippocampus significantlyenhanced(P＜0.05).⑥The testing result of immunohistochemistryshowed: PKA's expression of model group's hippocampus wasobviously lower than sham-operated group, and the differencewas significant(P＜0.01); Compared with model group, PKA'sexpression of electro-acupuncture obviously increased(P＜0.05).⑦The testing result of immunohistochemistry showed: Comparedwith the sham-operated group, it was significant that CREB'sexpression of model group's hippocampus decreased obviously(P＜0.01); Compared with model group, CREB's expression ofelectro-acupuncture group's hippocampus enhanced significantly(P＜0.05).⑧The testing result of hybridization showed:Compared with sham-operated group, it was significant thatNMDAR1mRNA's expression of model group's hippocampus decreasedobviously(P＜0.01); Compared with the model group, NMDAR1 mRNA's expression of electro-acupuncture group's hippocampus increasedsignificantly(P＜0.01).Conclusions: Bilateral hippocampal Aβ25-35 one-time inject-tionof the preparation of rat model successfully simulates thebehavior characteristic, in hippocampal neurons, Glu-NMDARsignaling pathway and cAMP-PKA-cREB signaling pathway involvedin learning and memory impairment of AD process. And electro-acupuncture"Shenshu" point, "Neiguan" point and "Dazhui"point AD can significantly improve learning and memory in rats. Its mechanism may be achieved through the following means:Reduce Glu neurotoxicity, protect the hippocampal neurons andincrease the expression of NMDAR1-mRNA, make full activationof NMDAR, improve the Glu-NMDAR signaling pathway conduction,at the same time enhance cAMP, PKA and CREB's expression ofhippocampal neurons, activate the cAMP-PKA-CREB signalingpathway in order to enhance LTP and improve the learning-memorycapacity. Acupuncture has proved once again that multi-target,multi-channel, multi-strata, the overall characteristics ofthe treatment can effectively alleviate the damage ofhippocampal neurons in AD rats so as to facilitate the signaltransduction pathway related to learning and memory normally,enhance the learning and memory of AD rats.
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