GENETIC ANALYSIS OF NEUROTRANSMITTER RECEPTORS IN AGING

哺乳动物物种的衰老过程包括显着的年龄相关 中枢神经系统功能的变化随着 神经递质受体作为正常和正常人的共同病因 衰老的病理性疾病，包括阿尔茨海默病。角色 衰老过程中血清素（5-羟色胺；5-HT）神经传递的影响 证明多种 5-HT 选择性受体与年龄相关的下降 前脑和脑干区域的亚型和 5-HT 转运蛋白， 包括额叶皮质、海马和中缝背核。至 日期，不同血清素能的细胞和分子特征 整个生命周期的结合位点尚未与相关的 遗传标记。此外，多巴胺神经传递的作用， 特别是多巴胺转运蛋白，虽然被证明会下降 与衰老有关，尚未与相关遗传标记相关。 因此，这些研究将解决多种神经药理学问题 5-HT 受体以及 5-HT 和 DA 转运蛋白以测试 假设中枢受体功能与年龄有关 与这些神经递质的遗传变异性相关 系统。 细胞和分子生物学技术将评估性别特异性 多种5-HT受体亚型的变化并比较5-HT和DA 一组 BXD 重组近交小鼠中的转运蛋白及其 祖细胞株与年龄（150、450 和 750 天）的关系。遗传 随后将进行分析以定位染色体 包含影响这些的数量性状位点（QTL）的区域 受体。最终，QTL 分析与 中枢血清素和多巴胺的神经药理学特征 选定大脑区域的结合位点，将允许测序 基因和这些基因的特定产物的鉴定 参与腹神经系统衰老。

Aging processes in mammalian species include significant age-related changes in central nervous system function with changes in neurotransmitter receptors as an etiology common to normal and pathological disorders of aging, including Alzheimer's disease. The role of serotonin (5-hydroxytryptamine; 5-HT) neurotransmission in aging has demonstrated an age-related decline of multiple 5-HT selective receptor subtypes and the 5-HT transporter in forebrain and brainstem regions, including the frontal cortex, hippocampus and dorsal raphe nucleus. To date, the cellular and molecular characteristics of diverse serotonergic binding sites across the lifespan have not been correlated with relevant genetic markers. Additionally, the role of dopamine neurotransmission, specifically the dopamine transporter, while demonstrated to decline with aging, has yet to be correlated with relevant genetic markers. Therefore, these studies will address the neuropharmacology of multiple 5-HT receptors as well as the 5-HT and DA transporters to test the hypothesis that age-related decline in central receptor function correlates with genetic based variability in these neurotransmitter systems. Cellular and molecular biological techniques will assess gender-specific changes in multiple 5-HT receptor subtypes and compare the 5-HT and DA transporters in a panel of BXD recombinant inbred mice and their progenitor strains with respect to age (150, 450 and 750 days). Genetic analysis will subsequently be performed in order to locate chromosomal regions containing the quantitative trait loci (QTL) which effect these receptors. Ultimately, pairing of QTL analysis with the neuropharmacologic characterization of central serotonin and dopamine binding sites in selected brain regions, will permit both the sequencing of genes and the identification of specific products of these genes involved in ventral nervous system aging.