Effect Of Early Intervention Of Electroacupuncture On Aβ Level In Brain Interstitial Fluid Of APP / PS1 Mice

BACKGROUNGAlzheimer’s Disease (Alzheimer’s diseases, AD) is a kind of occult onset, slow progress, the most common central nervous system degenerative diseases, the major clinical manifestations consist of early cognitive dysfunction, memory loss, personality changes and the language barrier, the late performance loss of memory, language, behavior ability, these seriously impact the patient’s daily behavior and social activities.Its pathological characteristics mainly include neural intracellular Neurofibrillary Tangles (NFT), neural extracellular Beta-Amyloid Protein (Aβ) deposition, and the Senile plaques, cerebral amyloid angiopathy (CAA) selective neuron lost, Synaptic damage, etc.The etiology and pathogenesis of AD has not yet completely clear. Theories About the cause of AD, mainly include β-Amyloid protein cascade theory, abnormal tau protein modification theory, nerve cell apoptosis theory, oxidative stress and gene mutation theory, etc. at present, P-Amyloid protein cascade theory occupies the mainstream status.To prevent the neurotoxicity caused by A(3 stranded and misfolding occurs in the brain, keep Aβ’s produce and clear in the dynamic balance is the key. The study of AD treatment strategy gradually formed a viewpoint of "early detection, early intervention, maintain the normal level of AP in the brain environment".OBJECTIVE:To investigate the effect of electroacupuncture(EA) therapy on the hippocampus and the brain interstitial fluid(ISF) A β 1-42 dysfunction of early pathological process of AD, which may be part of mechanism of EA therapy on Alzheimer’s disease(AD). In themeantime, finding out the effect of EA on the level of Aβ’s key transporter LRβ1 in APP/PS1 transgenic mice, explore whether there is a connection between the expression level of LRP-1 and Aβ.METHOD:Experiment 1:4 months old male APP/PS1 double transgenic mice were randomly divided into model group (n=8) and electroacupuncture group (n=8),4 months old male wild type (negativetransgenic) mice were used as normal control group(n=8). After 3 times treatment by EA therapy at GV20 and KI 1(15min per day,2/100Hz,0.5mA), at the meanwhile, themodel group & normal control group will be bounded under the same conditions butacupuncture, the concentration of AP1-42 in the hippocampus and its different change with the time in ISF was measured by Elisa. After microdialysis, sample on the left side of the fresh hippocampus in mice, with western bloting method to detect hippocampal tissue protein expression of LRP-1, analysis the correlation of LRP-1 level and the interventions in this experiment, if there is difference between groups.Experiment 2:4 months old male APP/PS1 double transgenic mice were randomly divided into model group (n=2) and electroacupuncture group (n=2),4 months old male wild type (negati vetransgenic) mice were used as normal control group. (n=2). After 3 times treatment by EA therapy at GV20 and KI 1 (15min per day,2/100Hz,0.5mA), at the meanwhile, themodel group & normal control group will be bounded under the same conditions butacupuncture.Hippocampal tissue section staining by flavin sulfur method, to observe the amyliod changes.RESULTS1. Interstitial fluid Aβ42 level’s change over time after acupuncture:Between 6-9 hours after the last time interventions, the level of soluble Aβ1-42 in same mouse’s hippocampus interstitial fluid samples have no significant difference. Thus, it can be concluded that between 6-9 hours after the short-term curative intervention, the level of soluble Aβ1-42 in the hippocampus interstitial fluid samples in A state of balance with no fluctuation.2. Hippocampus interstitial fluid Aβ1-42 level detection:Compared with normal control group, Model group’s hippocampus interstitial fluid Aβ1-42 level rises, and the difference was statistically significant (P<0.01); Compared with model group. Acupuncture group’s soluble Aβ1-42 level in the brain ISF was drop, and the difference was statistically significant (P<0.05). Suggests the possible of electric acupuncture’sbenign intervention on Aβ1-42 level of mouse brain ISF (lower).3. Hippocampus Aβ1-42 level detection:Compared with normal control group, the hippocampal tissue Aβ1-42 levels of model group has a statistical significance rise (P<0.01); Compared with model group, the Acupuncture group’s hippocampal tissue soluble Aβ1-42 level had a tendency to reduce, but there was no statistically significant difference (P>0.05). Suggest EA adjusts hippocampus ISF Aβ1-42 levels prior to the hippocampus tissue’s overall level of Aβ1-42. Presumably, EA lower levels of brain tissue AP may be the result of long-term cleared Aβin ISF.4. Hippocampus LRP-1 expression level:After the short-term EA or bound intervention, hippocampus LRP-1 expression differences between the three groups have no statistical significance (P> 0.05).CONCLUSION:1. Aβ1-42 Elisa results show that the genetically modified mice successfully simulates the AD amyloid pathological changes.2. After intervention, hippocampus interstitial fluid Aβ1-42 level was drop, this change prior to the change of hippocampus tissue’s overall level of AP 1-42. Presumably, EA lower levels of brain tissue Aβ may be the result of long-term cleared Ap in ISF.