The goal of the Animal Core is to provide support for each of the projects funded in the Program Project. In addition to standard responsibilities currently in progress, the Core will assume an additional responsibility to develop a colony of animals with the Tgr mutation (rGHRH-hGH) in a Brown-Norway genetic background. This will include characterizing the transgenic animal model for aging studies and detailing the basic characteristics of adult onset growth hormone deficiency in transgenics as compared to wild-type animals. This will be accomplished by infusing growth hormone-releasing hormone (GHRH) into the Tgr rat to ensure similar growth characteristics compared to wild-type animals. Growth hormone deficiency will then be induced in adulthood by withdrawal of GHRH infusion. We propose that growth hormone deficiency induced in adulthood will result in alterations in a number of parameters associated with age including, but not limited to, a decrease in plasma IGF-1 levels. rarefaction of brain vasculature, synaptic loss, alterations in axonal and dendritic architecture, and cognitive deficits. Specific aspects of adult- onset growth hormone deficiency using these animals will be assessed by the individual projects. The Animal Core has multiple aims. 1) The Core will procure and maintain animals used by program investigators and meet all AAALAC and institutional standards for animal care in the satellite facilities. The Core also has the responsibility of implanting animals with intracerebroventricular cannulae with osmotic mini-pumps for short- term (28 days) administration of IGF-1. 2) The core personnel will assess basic parameters of aging animals (general health and body weight), monitor sentinel and experimental animals for presence of disease and provide these data to project investigators. 3) The Core will develop a model for adult-onset growth hormone deficiency. Initial studies will validate the utility of the Tgr (Transgenic growth retarded) rat as a model appropriate to study brain aging. 4) The Core will provide statistical support for collaboration in the design of studies, data management, and statistical analyses of within project and between project results. The Animal Core is an essential aspect of the Program Project ensuring effective management of limited resources, smooth interactions between projects and the use of animal models that have been validated for studies of the biology of aging. In addition, the Core will be responsible for facilitating interactions with external/internal consultants and assisting in maintaining the focus of individual projects and the overall program.
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