OLFACTORY DEGENERATION--A MODEL

为了了解人类大脑的衰老和神经退行性变， 与老年痴呆症等衰老有关， 越来越明显的是，对衰老机制的广泛理解必须 通过对各种脊椎动物的研究获得的。 这些数据来自 这些动物模型将可能定义广义和专业 嗅觉系统老化的各个方面，并提供有关 影响退化过程的分子因素。 我们建议 采用了一种新的令人兴奋的模型进行嗅觉老化研究，即鲑鱼。 我们的发现促使了拟议的研究：1）我们的抗体 阿尔茨海默氏淀粉样前体蛋白（APP）的羧基末端 识别鲑鱼脑中的膜相关蛋白，2）抗APP （Boehringer-Mannheim）识别鲑鱼脑蛋白，3）银鲑 在限制饮食的情况下培养的婴儿不会在三岁时死亡， 五岁时还活着 4)嗅觉细胞的培养物 作为研究细胞因子和生长因子的模型系统， 以及增强剂，如褪黑激素，和5）北极研究所 生物学研究人员已经证明，体内透析可以进行 吃鲑鱼 因此，我们建议研究正常的3岁儿童回家 移民以及养殖鲑鱼在3和5岁， 蛋白质在快速衰老过程中形态变化中的作用。 的 将在这些群体中确定以下参数：1）数量 2）各种生长因子的数量及其在细胞内的分布 迁移过程中的受体，使用免疫化学和定量受体 放射自显影; 3）高尔基体的树突形态学变化 法 我们将开发一个鲑鱼嗅觉细胞的细胞培养系统， 以及设计体内实验。 格哈特医生有广泛的 使用体内方法研究神经化学物质变化的经验 如血清素、褪黑激素、多巴胺和去甲肾上腺素。 e将直接 我在神经化学和神经药理学领域的训练 鲑鱼嗅觉系统模型的发展。 此外， 长期目标是开展一些人类临床研究， 嗅觉老化在高纬度人口，如费尔班克斯。

In order to understand aging of the brain in man and the neurodegeneration associated with aging such as Alzheimer's disease, it has become increasingly evident that a broad understanding of aging mechanisms must be obtained by studies of a wide spectrum of vertebrates. Such data from these animal models will likely define both generalized and specialized aspects of aging in the olfactory system as well as providing insights into molecular factors which affect degenerative processes. We propose to employ a new exciting model for olfactory aging research, namely salmon. The proposed studies are prompted by our finding that: 1) our antibodies to the carboxyl terminal of the Alzheimer amyloid precursor protein (APP) recognize membrane associated proteins in salmon brain, 2) anti-APP (Boehringer-Mannheim) recognizes salmon brain proteins, 3) coho salmon cultured on a restricted diet do not die at the age of three years but are still alive at the age of five years. 4) Cultures of olfactory cells have been reported as model systems for studying cytokines and growth factors as well as potentiators, such as melatonin, and 5) an Institute of Arctic Biology researcher has demonstrated that in vivo dialysis can be carried out on salmon. We, therefore, propose to study normal 3-year-old homeward migrants a well as cultured salmon at 3 and 5 years of age with respect to the roles of proteins in morphological changes during rapid aging. The following parameters will be determined in these populations: 1) quantity and distribution of APP, 2) quantity of various growth factors and their receptors during migration using immunochemistry and quantitative receptor autoradiography, and 3) dendritic morphological changes with the Golgi method. We will develop a cell culture system for salmon olfactory cells, as well as design in vivo experiments. Dr. Gerhardt has extensive experience in using in vivo methods to investigate change in neurochemicals such as serotonin, melatonin, dopamine, and norepinephrine. e will direct my training in the areas of neurochemistry and neuropharmacology as applied to the development of a salmon model for the olfactory system. Also, a long-term goal would be to develop some human clinical research on olfactory aging in a high latitude population such as Fairbanks.