| Objective:To explore the changing process of spatial learning and memory ability and the brain white matter of the APP/PS1 transgenic mice,and the effect of changing white matter on the spatial learning and memory ability of the mice was also investigated.Methods:In this study,12 APP/PS1 double-transgenic mice were in APP/PS1 group,and 12 littermate wild-type mice were in WT group.When the mice were 2,4,6 and 12 month old,Morris water maze test was used to evaluate spatial learning and memory ability,and diffusion tensor imaging(DTI)was used to observe the changes of the white matter of the mouse brain.Three regions of interest were selected as corpus callosum,internal capsule and the fimbria,and the FA value of the three brain regions were calculated by itk-snap software at the 4 months.After the water maze test and magnetic resonance imaging when the mice were 12 month old,the brains of the mice were collected.Immunofluorescence was employed to observe the changes of the myelin basic protein(MBP)in the regions of the white matter of the mice.Results:1.Morris water maze test of mice in 2 groups at different ages:comparison between groups showed that,there was no significant differences in escape latency and the times passing through the position where the platform had lacated of the 2 groups(P>O.05),when the mice were 2 and 4 month old;The escape latency was increased for the mice in APP/PS1 group in the fourth day navigation experiment(P<0.05),and the the times passing through the platform were decreased compared with mice in WT group(P<0.01),when the mice were 6 month old;The mice in APP/PS1 group showed increased escape latency(P<0.05),and less times passing through the platform compared with mice in WT group(P<0.01),when the mice were 12 month old.Comparison in groups:with the increase of month,the escape latency of APP/PS1 mice was significantly prolonged at 6 and 12 month old(P<0.05),and the times of crossing platform decreased(P<0.01).The escape latency and the times crossing the original place of the platform did not change significantly in WT group(P>0.05).2.The DTI results of white matter in 2 groups:In corpus callosum region,comparison between groups showed that:there was no significant difference in FA of the 2 groups when the mice were 2,4 and 6 month old(P>0.05).When the mice were 12 month old,the FA value of APP/PS1 group was significantly decreased than WT group(P<0.01).Comparison in groups:the FA value of the corpus callosum decreased significantly when the APP/PS1 transgenic mice were 12 month old compared with 6 month old mice(P<0.01).In the regions of bilateral internal capsule and the fimbria,comparison between groups showed that there was no significant difference in the FA values of the 2 groups at 2,4,6 and 12 month old(P>0.05).And there was no significant difference in comparison in groups(P>0.05).3.The correlation between FA value and spatial learning and memory ability in corpus callosum area of 12 month old APP/PS1 mice:there was significant correlation between FA value and escape latency in the fourth day in water maze test(r=-0.658,P<0.05).There was no significant correlation between the FA value and the times crossing through the position where the platform had lacated in fifth day in the water maze test(r=0.589,P<0.05).4.The MBP immunofluorescence results of 12 month old mice showed that:in the corpus callosum,the expression of MBP in APP/PS1 group was significantly less than that in WT group(P<0.05);In the brain regions of internal capsule and the fimbria,the expression of MBP in the APP/PS1 group was not significantly different from that in the WT group(P>0.05).Conclusion:With the increase of age,the spatial learning and memory ability of APP/PS1 transgenic mice gradually deteriorated.The breakdown of the white matter integrity of the corpus callosum may be one of the reasons for the decline of the spatial learning and memory ability of the APP/PS1 mice. |
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