英文版实验计划书2英文版实验计划书2.pdfVIP

Principal Investigator/Program Director (Last, first, middle): Ye, Xuemin . a. Specific Aims: In the context of our aging population and with the advent of variant Creutzfeldt-Jakob disease (vCJD), there have been increased concerns surrounding transmissible spongiform encephalopathies (TSE). TSE primarily affect the central nervous system. Kuru, Creutzfeldt-Jakob disease (CJD), fatal familial insomnia and Gerstmann-Straussler syndrome (GSS) and vCJD are TSE found in human. It is still unknown why CJD affect primarily older patients. We hypothesize that the susceptibilities to TSE agents is different between young and old. To test our hypothesis, SAMP8, an animal model used for ageing research, will be used in this project. The aims of this project are (1) to compare susceptibilities to a mouse adapted scrapie agent (ME7) in brains of an aging accelerated mouse strain (SAMP8) vs. an aging resistant mouse strain (SAMR1); (2) to assess the following parameters in young (2 months) and aging (10 months) infected and control SAMP8 and SAMR1 mice: scrapie incubation period, body weight, prion protein accumulation, astrocytosis, vacuolation and periodic acid-schiff positive granular structures (PGS). By infecting SAMR1 and SAMP8 at 2 months and 10 months of age with the ME7 scrapie agent, and using histological and immunohistological methods, we will assess possible combination effects between the accelerated aging phenotype and TSE-induced effects on the above parameters. Analysis of the difference in susceptibilities and in changes induced in the young and aging nervous system to TSE agents may lead to strategies for prevention and or treatment of TSE diseases. b. Background and Significance: Scrapie is a fatal degenerative disease affecting the central nervous system of sheep and goats (Dickinson, 1976). It is the archetype of the TSE group of diseases that includes “Mad Cow Disease” or bov