The Effect And Mechanism Of Acupuncturing DU1 For Learning And Memory

ObjectivesTo evaluate the effect of acupuncture for children with intellectual disability by the method of systematic review and the influence of acupuncturing DU1 for learing and memory.(?)To explore the changes of functional connectivity of hippocmpus at acupuncturing DU1 by resting-state fMRI.To study the molecular mechanism of acupuncturing DU1 for HIBD rats by measuring the protein levels on the signal transduction of CREB in the hippocampus of the models.MethodsPart Ⅰ.We searched randomied controlled trials(RCTs)about acupuncture with rehabilitation training for children with Intellectual disability in the databases of Medline,CNKI,Wanfang,VIP and the Cochrane Controlled Trial Register from Jan.1973 to Apr.2016 and evaluated the bias risk of the included RCTs according to the Cochrane Handbook 5.1.0.The Review Manager 5.3.5 was used for data analysis.Part Ⅱ.8 healthy controls were scaned by Siemens 3.0 MRI in resting-state to collect the cerebral images before and after acupuncture.The functional connectivity of the whole cerebral with hippocmpus were tested by seed point correlation analysis.Part Ⅲ.80 seven days SD rats were randomly assigned into five groups:acupuncturing DU1 group(Group A),blank control group(Group B),surgical control group(Group C),non-point control group(Group D)and sham-operated group(Group E).The HIBD models were established by the method of RICE on group A,group C and group D.Every group was intervened separately for 4 weeks.Every rat was tested by Morris water maze after intervention.The protein expression of CREB,p-CREB,ERK,p-ERK of left hippocampus were measured by immunohistochemical analysis and western-blotting.The relative gene expression of microRNA-134 of left hippocampus was measured by quantitative real-time PCR.Results:Part Ⅰ.10 trials involving 561 patients were included.Data analysis showed that:①the clinical effective rate of the intervention group was better than the control group(RR=1.37,95%CI[1.21,1.56]),p<0.00001));②Meta analysis could not be used for FIQ and PIQ becuase of the high heterogeneity in the studies;③Acupuncture with rehabilitation training was better than rehabilitation training on improving VIQ by Gesell evaluation(WMD=12.85,95%CI[9.06,16.64],p<0.00001);④Acupuncture with rehabilitation training was better than rehabilitation training on improving social adaption by Gesell evaluation((WMD=8.45,95%CI[3.75,13.15],p=0.0004);⑤There was no difference between two groups on improving the Nerual and Mental development quotient.Part Ⅱ.After acupuncture,the functional connectivity of hippocmpus(R)with Precuneus(R)were increased,but the functional connectivities of hippocmpus(R)with Cerebellum Posterior Lobe(L),Precentral(L)and Superior Frontal Gyrus(R)were decreased.After acupuncture,the functional connectivity of Hippocmpus(L)with Temporal Lobe(R)were increased,but the functional connectivities of hippocmpus(L)with Fusiform Gyrus(L),Temporal_Inf(R),Frontal Lobe//Sub-Gyral(R)and Inferior Parietal Lobule(L)were decreased.Part Ⅲ.(1)Results of Morris water maze test:①The average escape latency after intervention of group C was significant longer than which of group A,group B and group E(P<0.05).The latency of group A was significant shorter than which of group D(P<0.05).②the times of traversing the platform effectively of group B was significant more than group C and group D(P<0.05).(2)Results of immunohistochemical analysis:①The positive expression of CREB in left hippocampus of group C was significant lower than group A,group B and group E(P<0.05).The positive expression of group A was significant higher than which of group D(P<0.05).②The positive expression of ERK1/2 in left hippocampus of group C was significant lower than group A,group B and group E(P<0.05).The positive expression of group A was significant higher than which of group D(P<0.05).(3)Results of western-blotting:The protein expression of CREB in left hippocampus of group C was lower than group A,group B and group E(P<0.05).The CREB protein expression of group A was significant higher than which of group D(P<0.05).The protein expression of p-CREB in left hippocampus of group C was lower than group A,group B,group D and group E(P<0.05).There was no difference between group A and group D in p-CREB expression(P>0.05).The protein expression of ERK1/2 in left hippocampus of group C was lower than group A,group B,group D and group E(P<0.05).There was no difference between group A and group D in ERK1/2 expression(P>0.05).The protein expression of p-ERK1/2 in left hippocampus of group C was lower than group A,group B and group E(P<0.05).The p-ERK1/2 protein expression of group A was significant higher than which of group D(P<0.05).(4)Results of quantitative real-time PCR:The relative gene expression of microRNA-134 in left hippocampus group C was higher than group A,group B and group E(P<0.05).The relative gene expression of microRNA-134 of group A was lower than which of group D(P<0.05).Conclusions1.Acupuncture can improve the effects of rehabilitation for children with intellectual disability,but large and high quality RCTs are needed to perform to provide the higher grade evidence.2.Acupncturing DU1 could regulate the functional connectivities of hippocmpus with several cerebral areas which were related with learning and memory.This may be the mechanism of DU1 at treating intellectual disability diseases.3.Acupncturing DU1 could improve the function of learning and memory of HIBD rats.The mechamism was related with the signal transduction of CREB/ERK in the hippocampus,and microRNA-134 may regulate the transduction.