Effect of voluntary running exercise on oligodendrocytes in the medial prefrontal cortex of APP/PS1 mice
Objective:To investigate the effect of voluntary running exercise on the number,differentiation,maturation,and myelina-tion of oligodendrocytes in the medial prefrontal cortex(mPFC)of APP/PS1 double transgenic mice with Alzheimer's disease(AD).Methods:Male transgenic mice with AD,aged 10 months,were randomly divided into AD group and AD+running group(AD+RUN group),and in addition,wild-type littermates with the same age were randomly divided into normal group(WT group)and normal+run-ning group(WT+RUN group).The mice in the two running groups were given voluntary running exercise in running cage for 3 months,while those in the AD group and the WT group were not given any treatment.After running exercise,behavioral tests were performed for the mice of all four groups at the same time;the Morris water maze test was used to observe the spatial learning and memory abili-ties of mice,and Y maze was used to observe the working memory abilities of mice;the novel object recognition test was used to assess the cognitive and memory functions of mice;the unbiased stereological method and immunohistochemistry were used for accurate quan-tification of the total number of mature oligodendrocytes(CC1+)in mPFC,as well as the density of mature oligodendrocytes in limbic cortex and Ⅱ,Ⅲ,Ⅴ,and Ⅵ layers of mPFC;immunofluorescence assay and a laser scanning confocal microscope were used to observe the density of immature oligodendrocytes(PDGFα+/Olig2+)and the fluorescence intensity of myelin basic protein(MBP)as a myelin marker.Results:Compared with the AD group,the AD+RUN group and the WT group had significantly better performance in the Morris water maze,the Y maze test,and the novel object recognition test,and the AD group had a significantly lower fluorescence intensity of MBP in mPFC than the WT group(P<0.05),while the AD+RUN group had a significantly higher fluorescence intensity of MBP in mPFC than the AD group(P<0.001).The AD+RUN group had a significant increase in the total number of CC1+cells in mPFC compared with the AD group(P<0.05).Compared with the AD group,the AD+RUN group had a significant increase in the density of CC1+cells in Ⅲ and Ⅴ layers of mPFC(P<0.05),and compared with the WT group,the AD group had a significant reduction in the density of CC1+cells in Ⅴ and Ⅵ layers of mPFC(P<0.05).Compared with the WT group,the AD group had a significantly higher density of PDGFα+/Olig2+cells in mPFC,and compared with the AD group,the AD+RUN group had a significantly lower density of PDGFα+/Olig2+cells in mPFC(P<0.05).Conclusion:Voluntary running exercise can promote oligodendrocyte differentiation and myelination in AD mice,which might be related to the result that exercise can improve the learning and memory abilities of APP/PS1 transgenic AD mice.