电针介导AFG3L2对阿尔茨海默病小鼠学习记忆能力的影响及其作用机制OA

Objective To observe the effects of electroacupuncture(EA)at the Baihui(GV20)and Shenting(GV24)acu-points on learning and memory function in Alzheimer disease(AD)mouse models,and to explore the underlying mechanisms.Methods A total of four male 5×familial Alzheimer disease(5×FAD)and four female wild-type(WT)mice,all aged two months were selected and cross-breeding.After approximately one month,their offspring were genotyped.A total of 20 3-month-old off-spring identified as positive were randomly assigned using a random number table to control group and EA group,with 10 cases in each group.Additionally,ten 3-month-old negative littermates were selected as the WT group.Following one week of adaptive fixa-tion,the EA group was administered electroacupuncture at the Baihui(GV20)and Shenting(GV24)acupoints with a needle penetra-tion depth of 2 mm,using a dense-sparse waveform at a frequency of 1/20 Hz for 30 minutes daily,five days a week for four weeks.The WT and control group were captured and fixed under the same conditions without receiving any other treatment.Novel location recognition test(total travel distance,discrimination index)was employed to evaluate learning and memory function;a 7.0 T small animal magnetic resonance imaging system was used to performe chemical exchange saturation transfer(CEST)imaging scans to de-tect glucose metabolism levels(asymmetric magnetisation transfer ratio[MTRasym(Δω)])in the hippocampus of mice.Immunohisto-chemistry was used to detect the amyloid-β(Aβ)positive area in the hippocampus of mice.Adenosine triphosphate(ATP)assay kit was used to detect the concentration of ATP in the hippocampus of mice.Immunofluorescence was used to detect the positive area of essential mitochondrial calcium uniporter regulator(EMER)in the hippocampus of mice.Western blot was used to detect the ex-pression levels of mitochondrial calcium uniporter(MCU)and AFG3 like matrix AAA peptidase 2(AFG3L2)proteins in the hippo-campus of mice.Results(1)Novel location recognition test:on the 2nd and 3rd day after intervention,there was no statistically significant difference in the total travel distance in all three groups(P＞0.05).Compared with the WT group,discrimination index in the control group decreased significantly on the 2nd and 3rd day after intervention(P＜0.05).Compared with the control group,dis-crimination index in the EA group increased significantly on the 2nd and 3rd day after intervention(P＜0.05).(2)Aβ positive area:compared with the WT group,the Aβ positive area in the hippocampal cornu ammonis 1(CA1)and dentate gyrus(DG)regions in the control group increased significantly after intervention(P＜0.05).Compared with the control group,the Aβ-positive area in the hippo-campal CA1 and DG regions in the EA group decreased significantly after intervention(P＜0.05).(3)MTRasym(Δω):compared with the WT group,hippocampal MTRasym(Δω)in the control group decreased significantly after intervention(P＜0.05).Compared with the control group,hippocampal MTRasym(Δω)in the EA group increased significantly after intervention(P＜0.05).(4)ATP concentration:compared with the WT group,ATP concentration in the hippocampus of the control group decreased significantly after intervention(P＜0.05);compared with the control group,ATP concentration in the hippocampus of the EA group increased sig-nificantly after intervention(P＜0.05).(5)EMER positive area:compared with the WT group,EMER positive area in the control group increased significantly after intervention(P＜0.05);compared with the control group,EMER positive area in the EA group decreased significantly after intervention(P＜0.05).(6)MCU and AFG3L2 protein expression levels:compared with the WT group,MCU protein expression level in the control group increased significantly after intervention(P＜0.05),while AFG3L2 protein ex-pression decreased significantly after intervention(P＜0.05).Compared with the control group,MCU protein expression level in the EA group decreased significantly after intervention(P＜0.05),while AFG3L2 protein expression increased significantly after inter-vention(P＜0.05).Conclusion EA at the Baihui(GV20)and Shenting(GV24)acupoints can improve learning and memory func-tion in mouse models with AD.The specific mechanism may involve improving hippocampal glucose metabolism and regulating AFG3L2 and related mitochondrial proteins.