Behavior, inflammatory response and cell autophagy of amyloid precursor protein / tau protein /presenilin-1 transgenic AD mice / 中华神经医学杂志

ABSTRACT

Objective To explore the behavior characteristics ofamyloid precursor protein / tau protein / presenilin-1 (APP/Tau/PS1) transgenic mice in different months of age and study the progress of inflammation and the changes of autophagy level in brain of these APP/Tau/PS1 Alzheimer's disease(AD) mice.Methods Four-month-old wild-type (WT) mice (B6:129SF2/J) and Tau/APP/PS1 transgenic mice at 2,4,6,8 and 12 months old (n=8) were chosen in our study.Morris water maze was used to detect the spatial learning and memory abilities ofAPP/Tau/PS1 AD mice.After the paraffin section,immunohistochemical fluorescence technology was used to detect the expression and distribution of glial fibrillary acidic protein (GFAP) in the brain of mice in the above 6 groups.The expression changes of GFAP,CD45 (inflammation marker) and LC3 (autophagy marker) in the hippocampal tissues of 6 groups were detected by Western blotting.Results In the morris water maze test,the escape latency increased obviously following the increasing of months:the latency of 6 months old mice was significantly prolonged as compared with that of 2 months old mice (P＜0.05),which was further significantly increased in 12-month-old mice (P＜0.05).In the exploring experiment,with the increasing of months,the times of crossing the original table in mice showed a trend of decline,time ofresidencing in the original platform quadrant was significantly reduced.As compared with that in the WT mice,the GFAP expression in the hippocampus of 8 and 12 months old AD mice was significantly increased (P＜0.05); meanwhile,the GFAP expression in 8-month-old mice was also significantly higher than that in 2 months old AD mice (P＜0.05).The CD45 expression in 6 months old AD mice was obviously increased as compared with that of WT mice (P＜0.05).As to the level of LC3-Ⅱ/Lc-Ⅰ,there was a significant increase in 2 months old AD mice as compared with WT mice (P＜0.05),which was further increased in 4 months old AD mice (P＜0.05),but decreased in 6 and 8 months old AD mice.Conclusion With the gradually loss of the leaming and memory abilities,inflammatory reaction is significantly increased,and the autophagy level increases at first,and then,decreases in the brain ofAPP/Tau/PS1 AD mice.