GENETIC ANALYSIS OF NEUROTRANSMITTER RECEPTORS IN AGING

哺乳动物物种的衰老过程包括与年龄相关的重要 中枢神经系统功能的变化， 神经递质受体是正常和 老年病理性疾病，包括阿尔茨海默病。的作用 5-羟色胺（5-hydroxytryptamine; 5-HT）神经传递的老化， 显示了多种5-HT选择性受体的年龄相关性下降， 亚型和前脑和脑干区域的5-HT转运体， 包括额叶皮层海马体和中缝背核到 日期，细胞和分子特征的不同， 整个生命周期的结合位点与相关的 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， 随着年龄的增长，尚未与相关的遗传标记相关。 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 年龄相关中枢受体功能下降假说 与这些神经递质的遗传变异性有关 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重组近交系小鼠中的转运蛋白及其表达 祖菌株相对于年龄（150，450和750天）。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基因座（QTL）的区域 受体。最终，QTL分析与 中枢5-羟色胺和多巴胺的神经药理学特征 在选定的大脑区域的结合位点，将允许测序 以及这些基因的特定产物的鉴定 参与腹神经系统的老化

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.