AMPA Receptor-mediated Mechanism In Hippocampal Neurons Of Alzheimer’s Disease Mice By Acupuncture Therapy Correlated To Synaptic Plasticity

Objective:To observe the effect of AMPA receptor mediated mechanism on synaptic plasticity in hippocampal neurons of Alzheimer’s disease mice enhanced by acupuncture therapy.Methods:The learning and memory function of9-month-old male SAMP8and SAMR1mice was assessed by using a Morris water maze(MWM) test.SAMP8mice showed poor learning and memory ability were taken as animal models of AD,and randomly divided into model group and acupuncture group.SAMR1mice with normal learning and memory ability were used as control group.The treatment of acupuncture on DU20(Baihui) and K1(Yongquan) was applied once daily,7days as a treatment course,lasted for4courses with2days interval between courses.Mice were sacrificed after treatment,their brains were isolated.Transmission electron microscope combining with stereological method was used to observe and measure.the synaptic ultrastructure in hippocampal neurons of CA1subregion.Western blot and immunohistochemistry combining with image analysis were used for the quantitative and locational studies of subunits GluRl,GluR2of AMPA receptors and the phosphorylation of GluR1and CaMK II.Results:1. Compared to the control group, mice in acupuncture group and model group showed a poor searching efficiency (p<0.05), prolonged escaping latency (p<0.05) increased path length (p<0.05) in place navigation test(PNT),and descendent time (p<0.05) and length percentage (p<0.05) in the target quadrant,decreased site (p<0.05) and target annulus crossings (p<0.05) in spatial probe trail(SPT),witch indicated the spacial learning and memory ability of the mice in model group and acupuncture group was obviously declined.2. In comparison to the control group, the thickness of PSD (p<0.05) and the curvature of synaptic interface (p<0.05) decreased,the width of synaptic space increased (p<0.05) in hippocampal neurons of CA1area in the model group.while the thickness of PSD (p<0.05) and the curvature of synaptic interface (p<0.05) was increased,the width of synaptic space decreased (p<0.05)3.There were no significant differences in the total amount of GluRl in hippocampus among the three groups (p>0.05),while compared to the control group.the GluRl content in the CA1subregion in model group was declined (p<0.05),which in acupuncture group was upregulated (p>0.05)In comparison to the control group,the GluR2quantity in hippocampus and in CA1area in model group were dicreased (p<0.05),which were upregulated in acupuncture group (p<0.05)There were no significant differences in the total quantity of the phosphorylated GluR1and phosphorylated CaMKⅡ in hippocampus among the three groups (p>0.05).while the level of phosphorylated GluRl in the CA1subregion in model group was lower than the control group (p<0.05), which was upregulated in acupuncture group (p>0.05)Conclusions:1.The decrease in the number of AMPA receptor and the pathological remodeling in AMPA receptor subtype in hippocampal CA1area associated with AD provided a new neurobiology evidence for the usefulness of SAMP8as a excellent animal model for AD.2.Acupuncture had a effect of facilitate the synaptic plasticity in hippocampal neurons of SAMP8mice.3.Regulating the quantity and subtype of AMPA receptor in hippocampal neurons, strengthening the synaptic transmission capability,to facilitate the ability of memory acquisition and consolidation would be the therapeutic mechanism of acupuncture for AD treatment.