application) The goal of the Animal Core is to provide animal-related resources to support this PPG in the following aims: 1) to provide a central facility for the purchase and care of Sprague Dawley rats needed for Projects 1-4 and Core B (Cell Culture Core), 2) to provide Projects 2 and 4 with animals rendered cholinergically dysfunctional by fimbrial lesions, 3) to provide projects 1,3, and 4 with aged and genotyped mice that overexpress both amyloid precursor protein (APP) and presenilin 1 (PS1), 4) to provide Projects 3 and 4 with standardized histochemical immunocytochemical analyses of gene transfer efficiency and function in brain tissues, and 5) to provide Projects 1-4 with a core facility for stereological analyses of marker-density in brain regions labelled in Aims 3 and 4 above or in their own studies.
These aims are modified from the previous funding period in several significant manners. The application has been augmented by the addition of an important model for the overexpression of gene products associated with Alzheimer's disease: APP and PS1. This model will serve to test the actions of novel drugs and gene-therapies on brain function, and to determine how over-expression of these Alzheimer's type products affects the ectopic expression of somatic transgenes administered virally or nonvirally. Another modification involves a greater emphasis on neuroprotection models, with reduced emphasis on behavioral studies. This focus on studying the protective actions of variety of potential therapeutic actions is accompanied by a new stereological set-up that will permit regular unbiased quantification of markers in brain tissue.
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