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A Study Of Animal Model With Alzheimer's Disease

Posted on:2006-01-18Degree:MasterType:Thesis
Country:ChinaCandidate:Y YangFull Text:PDF
GTID:2144360182460332Subject:Health Toxicology
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Objective:To establish the AD rat model through the method of pretreatment with aluminum chloride by intrathecal injection (IT), also to constast with the method of pretreatment with aluminium chloride and D—Galactose by intraperitoneal injection (IP), and to evaluate these two methods.Methods: 12-month-old SD rats were divided into three experiments. Model groups rats administrated with aluminum chloride by intrathecal injection (for 5 days).First,IT diverse concentrations of AlCl3 for the appropriate concentration. Second,get the brains in diverse periods for the appropriate one.Third,under this two conditions try to establish the models again. 12-month-old SD rats administrated with aluminum chloride and D—Galactose by intraperitoneal injection to establish AD models .To make paraffin section after behaviour test,The alternation of rat's behaviour and the expression of β-APP, β-AP, tau in cerebral cortex and hippocampi was observed with behaviour test and ABC immunocytochemical methods. Silver staining by a modified Bielschowsky method for NFTs and ABC immunocytochemical method of beta-amyloid for SPs and histochemistry of Cerebral cortex and hippocampi for GVD. Results: the method of pretreatment with aluminum chloride by intrathecal injection:we got the appropriate concentration( 1.5%) and the appropriate time of biomaterial collection (total 33 days); we made the model successfully by the two conditions. The behaviour test results showed that the frequency of electric shock was increased, incubation period was decreased in model groups. β-AP, tau and β-APP expression significantly increased in cerebral cortex andhippocampus in model groups. Aluminum could result in the decrease of neurons in cerebrum, and pyramidal neurons in hippocampus. GVD of nerve cells in hippocampus were observed in each model group,the number of GVD cells in model group significantly increased. NFTs and A(3 deposit could be found in model groups. The method of pretreatment with aluminium chloride and D—Galactose by intraperitoneal injection induced neuron loss in both cerebral cortex and hippocampi. The number of GVD cells in model group increased significantly. The behaviour test results showed that the frequency of electric shock was increased, incubation period was decreased. J3-AP, tau andji-APP expression increased significantly in cerebral cortice in model rat's cerebrum. Conclusion: though the method of pretreatment with aluminium chloride and D-Galactose by intraperitoneal injection induced the changes which were some similar to behavior characterizations and some of pathological manifestation of human Alzheimer's disease, but cannot form NFTs and SPs. Also the interferential factors are complicated and the rate of ascites and death rate are higher than others.The method of pretreatment with Aluminum chloride by intrathecal injection significantly induced neuron loss in both cerebral cortex and hippocampi andp-AP^ tau and P-APP expression was increased significantly in AD-animal-moders cerebrum,especially can form NFTs andp-AP deposit. The method are superior to others and it is a simple and promising animal models in AD. The models can well represent behavior characterizations and some of pathological manifestation of human Alzheimer's disease.
Keywords/Search Tags:Alzheimer's disease, animal model, intrathecal injection, intraperitoneal injection, aluminum
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