The Effect Of Early Cognitive Training On The Ability Of Learning And Memory And Generalization Based On Multimodal MR Imaging In AD Model Mice

ObjectiveTo explore the effect of early cognitive rehabilitation training intervention on learning and memory and memory generalization ability of Alzheimer disease(AD)model animal APP/PS1 double transgenic mice;and use small animal multimodal magnetic resonance imaging analysis to reveal Imaging characteristics of early cognitive rehabilitation training on APP/PS1 mice's whole brain functional activities and changes in neurochemical metabolism in the brain.MethodsFive-month-old APP/PS1 mice were used as the research object.PCR was used to identify the genotypes of model mice.According to the random number table method,APP/PS1 double-transgenic mice were randomly divided into two groups: model group and cognitive rehabilitation training group.;Take the same litter negative genotype mice as the control group,8 in each group;the mice in the cognitive rehabilitation training group intervened with the cognitive rehabilitation training methods of scholars such as Talboom JS.Clues-platform conditional learning and memory "and" memory flexibility "two-stage training,the training is completed correctly 8 times a day,6 days a week,2 weeks in each stage,a total of 4 weeks,the other two groups adopt the same conditions Grab and return to the cage.The novel object recognition test and Morris water maze test were used to the learning and memory and memory generalization ability of mice in each group;the blood oxygen level dependent functional magnetic resonance imaging(BOLD-fMRI)of small animals was used)Scanning and regional homogeneity(ReHo)of the whole brain BOLD signal;using small animal magnetic resonance spectroscopy(MRS)scanning to analyze the N-acetylaspartate(NAA),Glutamate(Glu),Choline(Cho)and myo-Inositol(mI)metabolism.Results(1)The changes in learning memory and memory generalization ability of APP/PS1 mice: new novel recognition experiment,wild group mice explore new objects longer than old objects(P=0.036),while model group and cognitive rehabilitation training group There is no difference in the exploration time between new and old objects between APP/PS1 mice(P>0.05),which indicates that the 5-month-old APP/PS1 mice have difficulty in exploring new objects,while wild-type mice are normal In a new object recognition experiment under a similar background,APP/PS1 mice in the model group and cognitive rehabilitation training group had memory generalization disorder(P<0.01 or P<0.05)compared with wild mice,but memory generalization between the two groups Ability was not statistically different(P>0.05),suggesting that APP/PS1 mice in the model group and cognitive rehabilitation training group had memory generalization disorder before cognitive rehabilitation training intervention,and the baseline was consistent;(2)The monitoring of cognitive rehabilitation training effect: The task of completion accuracy rate every day: in the cognitive rehabilitation training group,APP/PS1 mice in the clue-station conditioned learning,memory and memory flexibility training stage two,the task completion accuracy rate gradually increased with the learning days,and the learning accuracy rate of the two stages tended to be stable in the last 3-4 days(the accuracy rate was more than 80%).;(3)The effect of early cognitive rehabilitation training on learning and memory of APP/PS1 mice: Morris water maze experiment showed that compared with the wild group,the escape latency of the model group mice was significantly prolonged(P<0.001),and the number of crossing platforms was reduced(P<0.01);compared with the model group,the escape latency of mice in the cognitive rehabilitation training group decreased significantly(P<0.01),and the number of crossing platforms increased(P<0.05),indicating that early cognitive rehabilitation training effectively improved APP/PS1 mice learning and memory ability;(4)The effect of early cognitive rehabilitation training on memory generalization ability of APP/PS1 mice: Memory generalization test showed that compared with the wild group,the memory generalization ability of model group mice was significantly reduced(P<0.01),and Compared with the model group,the memory generalization ability of the cognitive rehabilitation training group was significantly improved(P<0.05),indicating that early cognitive rehabilitation training effectively improved the memory generalization ability of APP/PS1 mice;(5)The effect of early cognitive rehabilitation training on brain function activity: Compared with the wild group,the ReHo value of the model group mice was lower in the right hippocampus and bilateral medial prefrontal cortex(mPFC)(P<0.001);Compared with the model group,ReHo values of mice in the cognitive rehabilitation training group increased in the right hippocampus and bilateral mPFC(P<0.001).Correlation analysis of the brain area functional activity and memory generalization ability test behavior of all mice found that the escape latency of mice was negatively correlated with mPFC and hippocampus ReHo values,and the results were r =-0.441(P=0.035),R =-0.455(P=0.029);(6)The effect of early cognitive rehabilitation training on brain metabolites in APP/PS1 mice: Compared with the wild group,mice in the model group showed a decrease in NAA and Glu content,and a Increase in Cho,mI content in mPFC,hippocampus,and reuniens thalamic nucleus(P <0.001 or P <0.01 or P <0.05);compared with the model group,mice in the cognitive rehabilitation training group showed a increase in NAA and Cho content,and a decrease in Cho content in mPFC and hippocampus(P <0.001 or P <0.01 or P <0.05),and also showed a decrease in mI content in mPFC.(P <0.01 or P <0.05).ConclusionThe early cognitive rehabilitation training for 4 weeks can improve the learning and memory and memory generalization ability of APP/PS1 mice.The mechanism may be through the adjustment of functional activities of mPFC,hippocampus and other key brain regions and their neurological metabolism levels.