An Experimental Study For The Expression Of TRAIL In Hippocampus Of Rat With Alzheimer's Disease (AD) Induced By Aβ_25-35

Objective:To study the learning and memory impairment induced by amyloidβ-peptide25-35(Aβ_25-35) in rats,as well as the changes of expression of TRAIL protein, in hippocampus.Methods:(1) The experimental model of animal:Female Wistar rats with normal cognition,Aβ_25-35 was injected into bilateral hippocampus.They were made stereotaxically at coordinates P 3.5,L 2.0,V 3.0 below the surface of the skull from the fonticulus anterior.(2) The experiment of AD induced by Aβ_25-35 in rat:75 female rats were randomly divided into three groups:normal group,Aβgroup, estradiol(E₂) group.Aβ_25-35 lul(5ug) was injected into bilateral hippocampus in Aβgroup and estradiol group.Next day,estradiol was injected subcutanously in estradiol group.13 days later,to detect the praxiology of these rat by Morris water maze.At the end of experiment,the rat were decapitated,then brain was separated for examination of configuration and super microstructure by optic and electron miscroscope and expression of TRAIL protein by immunohistochemistry method.Results:1.The observation of cognition in AD rat:In Morris water maze test,Aβgroup compared with normal group,the avoiding latent period extended,the percentage of time in the platform quadrant and the time of crossing platform obviously decreased, P＜0.01;Compared with Aβgroup,the avoiding latent period of estradiol group shorten,the percentage of time in the platform quadrant and the time of crossing platform obviously increased,P＜0.05.2.By optical microscope,Aβ_25-35 induced hippocampal neurons to undergo apoptosis was observed in Aβgroup,including morphological changes of chromatin condensation,chromatin agglomerated formation,nucleus shrinkage.In estradiol group the apoptosis of neuron reduced;not only morphology of nucleus but also chromatin condensation.3.The expression of TRAIL in rat's hippocampus:After injected Aβ_25-35,the positive rate of TRAIL protein in rat's hippocampus of Aβgroup significantly increased,Compared with Aβgroup,the positive rate of TRAIL protein of estradiol group significantly decreased,P＜0.01.Compared with normal group,the immunoreactivity density of TRAIL protein of Aβgroup obviously increased,the immunoreactivity density of TRAIL protein in estradiol group compared with Aβgroup decreased,P＜0.05.Conclusions:There are significant deficits of cognition in AD rats model induced by Aβ_25-35,expression of hippocampal TRAIL in the rats increased.After the therapy of estradiol,expression of hippocampal TRAIL in the rats reduced,learn and memory function of the rats improved.AD is related with neurons apoptosis induced by TRAIL.Estradiol is used to the therapy of AD by its inhibition to neurons apoptosis induced by TRAIL.