Animal Model Of Alzheimer's Disease Induced By Aβ(1-40) Combined With 192-igg-saporin

Alzheimer's disease (Alzheimer's disease, AD) is the most common neurodegenerative disease, mainly in the elderly aged 65 and above. The clinical characteristics of insidious onset, gradual emergence of memory loss and cognitive dysfunction,abnormal behavior and social barriers. As China's growing aging population, Alzheimer's disease is increasingly becoming a serious social problem. According to surveys , China has 129 million population of more than 60 years, the elderly proportion of the total population has reached 10.15 percent, making China's advance into old age-based country with a population. It is noteworthy that the prevalence of senile dementia, accounting for about 60 years of age about 10% of the population, including Alzheimer's disease (AD) accounts for about 5% in China is estimated to have about 6.45 million patients. And for each additional 5-year-old age, AD will triple the prevalence in the 80-85 year-old patient in 20% of the elderly suffering from senile dementia , Following heart disease, cancer and stroke after the fourth leading cause of death to the patient family, society has posed a great burden and pressure. Thus, AD research has become an urgent issue in neuroscience.The main pathological features of AD are in the following three aspects (1) senile plaques (SP) formation, mainly extracellular deposition of Aβprotein in the system. (2) Neurofibrilary tangle(sNFT) formatted extracellularly , mainly cause by multiple and abnormal Tau protein phosphorylation. (3) Neural apoptosis mainly in the basal forebrain cholinergic neurons accompanied withγ-aminobutyric acid (GABA), Noradrenergic and 5 - hydroxytryptamine energy (5 -HT) neurons.Animal model of AD etiology and pathogenesis of AD as a basis of the study, there has never been an ideal animal model of AD model of the current construction method commonly used in the following categories: 1: external force injured model, such as cutting model, 2: Aβamyloid protein fragment model of intracerebral injection 3: excited drug injury basal forebrain cholinergic neurons in the model 4: Composite animal models 5: transgenic animal models. A variety of animal models , to some extent ,can be simulated part of the pathological features of AD, but still no animal model can be a more comprehensive simulation of all the pathological features of AD. Thus,AD has seriously hindered the progress of the study. This study centralized in the animal model created by intracerebroventricular injection of nerve immunotoxin 192-IgG-saporin and hippocampal injection Aβ1-40 fragment. Alzheimer's disease.Experimental part1 Materials and Methods32 SD male rats weighing 250-300g,were randomly divided into four groups , eight rats in one group respectly : normal group,Aβ1-40 group (Aβgroup),nerve immunotoxin 192-IgG-saporin group (192 group),nerve immunotoxin 192-IgG-saporin and Aβ1-40 combination group (combined group). Single later ventricle, and hippocampus were injected with 192-IgG-saporin 5μl (2.5μg/μl) and Aβ1-40 10μl (1μg/μl) respectively . The combined group were created by192-IgG-saporin and Aβ1-40 jointly. lateral ventricle according to coordinates: bregma, - 0.8 mm, the left side 1.5 mm, depth 5.5 mm hippocampus: bregma, -3.4 mm, the left side 2.5 mm, depth 4.5 mm. Two weeks later Y maze were tested.By the end of the test, perfusion,fixed to the brain,sugar dehydrated, frozen sections. Basal forebrain slices of ChAT immunohistochemical staining on the medial septum (MS), diagonal band vertical branch(VDB) of ChAT-positive neurons ,calculated the positive number. Hippocampus sections of cholinergic fibers (AChE),astrocyte cells (GFAP) immunohistochemical staining,Nissl staining,Congo red staining and Thioflavin -T fluorescence staining. Calculated the AChE-positive fibers and pyramid cells count, GFAP numbers analysis. All data were statistical analyzed with the SPSS13.0.2 ResultsThe results of Y-maze test shows that there are significant decline in all groups when comparied with the normal group(P<0.05),and no difference among the injuried groups (P>0.05).The aggragated Aβwere dected in the hippocampus of the Aβgroup and combined group by the congred and Thioflavin T staining at the same time. Compared to the normal group,the number of paramidal cells in the hippocampus of Aβgroup and the combined group were significantly reduced(P<0.05).Also,there was on decrease in the 192-IgG-saporin groups (P>0.05).. Aβ1-40 group and combined group in hippocampus of astrocyte cells proliferation (P <0.05) ,192-IgG-saporin group no significant proliferation (P> 0.05). 192-IgG-saporin and the joint group of cholinergic fibers markedly reduced (P <0.01), no significant change was oberserved in the the number of cholinergic fibers in group Aβ1-40 (P> 0.05). 192-IgG-saporin and the Joint Group on basal forebrain ChAT-positive cells significantly reduced (P = 0.000) , Aβgroup of basal forebrain ChAT-positive cells were no significant changes (P> 0.05).3 SummaryThe learning and memory ability of animal model created by Aβ(1-40)and immunotoxin 192-IgG-saporin has declined markedly,Basal forebrain cholinergic neurons in the number of significantly reduced.In the hippocampus,the number of pyramid cells were significantly reduced accompanied with AchE positive fibers and astrocyte proliferation .In short: the animal model of Alzheimer's disease created by Aβ1-40 combined with nerve immunotoxin 192-IgG-saporin can be more comprehensive than the single role of the analog AD pathological features, is an ideal animal model of AD.