Of The Comparison Of Morphological Characteristics Between Two Types Of Alzheimer's Disease (AD) Mouse Models And Effect Of Apo E Gene On Aluminum-induced AD

Objective:To compare the morphological characteristics and Aβprotein expression in brain tissue between the C57BL/6J mice and APP/PS-1 double-transgenic mice after infected with aluminum,to explore whether aluminum poisoning APP/PS-1 double transgenic mice composite model can better simulate the pathological changes of AD,to compare the morphological characteristics and Aβprotein expression in brain between aluminum poisoning Apo E knockout mice and C57BL/6J mice,and to explore the role of Apo E gene in aluminum-induced AD.Methods:According to body weight,16 healthy male C57BL/6J mice,16 APP/PS-1 double-transgenic mice and 16 healthy male Apo E knockout mice were randomly divided into 2 groups:control group(n=8) and experimental group(n=8).The mice in control group were injected with normal saline,while the mice in experimental group were injected through lateral ventricle 1.0%AlCl3 for 5 d,3μl per mouse.Then the mice were killed,and brain,bilateral cerebral cortex and hippocampus were gained for observing the morphological change.Immunohistochemistry was used to detect the expression of Aβprotein in the cortex and hippocampus.Results:HE staining results showed that larger quantities of cerebral cortex neurons were found in C57BL/6J mice,Apo E knockout mice and aluminum poisoning Apo E knockout mice,that hippocampal pyramidal cell layer were arranged regularly with neural larger element,nuclear circle,nucleolus Obviously,a clear cell outline.In aluminum- transfecting C57BL/6J mice,APP/PS-1 double-transgenic mice and in aluminum- transfecting APP/PS-1 double-transgenic mice the size of cerebral cortex nerve neuron became smaller,hippocampal pyramidal cell layer pyramidal cells showed sparse,loose,the level of confusion,there's serious injury scattered cells,is mainly expressed in the nucleus pyknosis was like,perinuclear and cytoplasmic vacuolation cell structure destruction and cell contours fuzzy.The vacuolated granule cell count of cortex and hippocampal neurons showed significant difference between 2 groups in aluminum poisoning APP/PS-1 double-transgenic composite models and aluminum poisoning C57BL/6J mouse model(P＜0.05),between aluminum poisoning APP/PS-1 double-transgenic composite modes and aluminum poisoning C57BL/6J mouse models (P＜0.05),between aluminum poisoning Apo E knockout mice and aluminum poisoning C57BL/6J mice(P＜0.05),but not between 2 group in Apo E gene knockout mouse models(P＞0.05). Silver staining results showed that several NFT was found in cerebral cortex and hippocampus of aluminum poisoning C57BL/6J mice,but not in C57BL/6J mice,Apo E knockout mice and aluminum poisoning Apo E knockout mice,while more intensive NFT was found in cerebral cortex of aluminum poisoning APP/PS-1 double transgenic mice.Compared with control group,the NFT-like change of neurons increased significantly in two model mice in experiment group(P＜0.05).The NFT-like change of neurons showed significant difference between aluminum poisoning APP/PS-1 double-transgenic composite model and aluminum poisoning C57BL/6J mouse model, between aluminum poisoning Apo E knockout mice and aluminum poisoning C57BL/6J mice(P＜0.05),but not between 2 group in Apo E gene knockout mouse models(P＞0.05).Congo red staining results showed that no SP was observed in cerebral cortex of aluminum poisoning C57BL/6J mice and Apo E gene knockout mice,but scattered immatured SP were,found in cortex and hippocampus of aluminum poisoning APP/PS-1 double transgenic mice.Aβprotein immunoreactive positive neurons were found in cell cytoplasm of pyramidal cell layer in cerebral cortex and hippocampus in all groups by immunohistochemical staining..Using Image-Pro plus 6.0 image analysis software analysis,integral optical density(IOD) of positive cells in the cortex the average was significantly different between 2 groups in aluminum poisoning APP/PS-1 double-transgenic composite model and aluminum poisoning C57BL/6J mouse model (P＜0.05),but not in Apo E gene knockout mouse model(P＞0.05).IOD was also significantly different between aluminum poisoning APP/PS-1 double-transgenic composite model and aluminum poisoning C57BL/6J mouse model,between aluminum poisoning Apo E knockout mice and aluminum poisoning C57BL/6J(P＜0.05).Conclusion:The aluminum can lead to morphological changes of cerebral cortex and hippocampal nerve cells in mouse,with AD-like pathological features.Aluminum poisoning APP/PS-1 composite double transgenic mouse model was better than simply C57BL/6J mouse model for simulating the pathological features of AD change.Apo E gene play a role in aluminum-induced AD,but the mechanism should be further studied.