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The Research Of Olfactory Changing In A Rat Model Of Alzheimer's Disease

Posted on:2010-01-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y Y ZhuFull Text:PDF
GTID:1114360275975363Subject:Otolaryngology
Abstract/Summary:PDF Full Text Request
Alzheimer's disease(AD) is a neurodegenerative disorder with pathologically characterized by the presence of senile plaques(SP),neurofibrillary tangles(NFT),decreasing of neurons and the granulovacuolar degeneration(GVD),as we know,the pathogenesis of AD is very complex.In some reports,olfactory dysfunction is present in the early stage of Alzheimer's disease.It is very important to set up an ideal model of AD to observed the change of pathology in olfactory systerm.In the present study,we set up the model by a single intracerebroventricular injection ofβ-amyloid peptide in rat brain. After injection of Aβ,the spatial memory of rats was significantly impaired in the Morris water maze.We found changing of neuropathology in the olfactory epithelium,olfactory bulb and hippocampi by colouration of the slice up.After the foundation of model,we test the expression of glial fibrillary acidic protein(GFAP),neuron-specific enolase(NSE) and olfactory marker protein(OMP) by immunihistochemistry in the olfactory epithelium,olfactory bulb and hippocampi of rats in control group and model group.Furthermore,we analysed the statistics meaning between control group and model group byt test.For the futher research of the change in gene level,we used microarrary analysis to study gene expression in the olfactory blub in the model of AD,for the aim to analyse the relationship between olfactory and AD in the level of gene.We identified 23 novel genes that were differentially expressed by the first filtration in 811genes,these genes include neurodegenerative disorder the pathway about apoptosis and calcium signaling and so on,which explained the relationship between the olfactory and AD.Some of these gene transcrips were futher analyzed by quantitative real-time reverse transcriptase polymerase chain reaction(RT-PCR) to validate date gathered from the DNA microarray analysis.In addition,we used Western Blot to validate the changing in the protein level include GFAP,NSE,OMP,Calcineurin and protein kinase C.We found that the differencess between control group and model group were obviously no mater in the level of mRNA or the level of proteins.In addition,the changes were consistented with the down-regulated or up-regulated in our microarray results.
Keywords/Search Tags:Rat, Alzheimer's disease, olfactory system, immunihistochemistry, gene expression profile
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