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The Selection Of Abnormal Expression Genes Of Senile Dementia By Gene Expression Profiling And The Effects Of Acupuncture On The Major Genes

Posted on:2004-02-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:X N FanFull Text:PDF
GTID:1104360095950475Subject:Acupuncture and Massage
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Senile dementia is a life process with multiple genes cooperated (antagonistic) actions. Its incidence is increasing rapidly. The definitive etiological factors are not known up to now. In this study, the mice gene expression profiling is used to screen the genes that are abnormally expressed in the senescence-accelerated-mice (SAM) brain samples, which are regarded as a replacing animal model for studying Alzheimer's disease. The roles of some genes abnormally expressed in the pathological and physiological mechanisms of senile dementia are also discussed. The mRNA expression changes of two genes, cyclin dependent kinase inhibitor 2b (P15) and calcineurin (CaN), with aging in the SAMP 10 were observed by Northern hybridization. The effects of acupuncture playing in different acupoint regions onto the expression levels of the two genes are investigated. The main results are below:1. The 2-month-old SAMP8 is selected as a control group compared with a 10-month-old SAMPS. We screen out 234 genes that are abnormally expressed, among which 146 genes are down-regulated and 88 genes are up-regulated. Among those down-regulated genes, 87 genes are logging in GenBank while among those up-regulated, 59 genes are logging in GenBank.2. The 10-month-old SAMR1 is selected as a control group compared with the 10-month-old SAMPS. We screen out 242 genes are abnormally expressed, among which 173 genes are down-regulated (among which 62 genes are logging in GenBank), while 69 genes are up-regulated (among which 68 genes are logging in GenBank).3. The 2-month-old SAMP8 and a/the 10-month-old SAMR1 are both selected as control groups compared with the 10-month-old SAMP8. We screen out 110 genes that are abnormally expressed, among which 79 genes are down-regulated (among which 30 genes are logging in GenBank), while 31 genes are up-regulated, and all are logging in GenBank. The down-regulated genes are mostly related to the pathological functions of releasing of synaptic vesicle, signal transduction, cell skeleton, energy metabolism, etc. On the other hand, the up-regulated genes are mainly involved in the pathology functions of cell cycle, ion channel, protein synthesis, inflammatory reaction, and so on.4. As a member of the same family with P16, which has been demonstrated as a major gene ofaging, the up-regulated expression of P15 mRNA disorders the modulation of cell cycle. This suggests that P15 could be a crucial factor leading to senile dementia. Thedown-regulation of CaN mRNA might break the dynamic balance of protein phosphorylation and dephosphorylation, through which CaN accelerates the formation of NHF and affects cells' normal functions such as signal transduction and gene transcription. So it's suspected that CaN might activate the occurrence and accelerate the development of senile dementia.5. Northern hybridization is used to study the changes of P1 5 mRNA with aging in the brain of SAMP 10. It is detected that the expression of P15 mRNA is up-regulated from the beginning of 6-month-old. Both acupuncture groups have the capacity of helping to down-regulate the abnormal expression of P15 mRNA in 8-month-old SAMP 10. The down-regulation role of ZBGS on P15 mRNA seems to be stronger than that of XNKQ. By depressing the expression of P15 mRNA, acupuncture might have the capacity of repairing the damaged DNA, lessening the cell apoptosis and delaying the speed of aging..6. By using Northern hybridization, the changes of CaN mRNA with aging is studied in the brain of SAMP 10. The expression level of CaN mRNA is the lowest at 6-month-old sample. Both acupuncture groups have the capacity of helping to up-regulate the abnormal expression of CaN mRNA in 8-month-old SAMP 10. The up-regulation role of XNKQ on CaN seems to be stronger than that of ZBGS. By elevating the expression of CaN mRNA. acupuncture might have improved the state and the level of balance that of phosphorylation and dephosphorylation, influenced the switching modulation of the ion channel, reg...
Keywords/Search Tags:senile dementia, senescence-accelerated-mouse, acupuncture, gene expression profile, cell cycle, protein phosphatase
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