GENETIC ANALYSIS OF NEUROTRANSMITTER RECEPTORS IN AGING
GENETIC ANALYSIS OF NEUROTRANSMITTER RECEPTORS IN AGING
批准号:
6359545
负责人:
JOAN M LAKOSKI
金额:
$15.75万
依托单位国家:
美国
项目类别:
财政年份:
2000
资助国家:
美国
项目状态:
已结题
起止时间:
2000-09-30 至 2001-01-31
关键词:
age difference aging autoradiography binding sites brain mapping brain stem dopamine transporter genetic markers in situ hybridization laboratory mouse neurochemistry neuropharmacology northern blottings phenotype prosencephalon quantitative trait loci receptor binding receptor expression serotonin receptor serotonin transporter
中文摘要
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。
英文摘要
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.
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会议论文
Clinical Research Scholars and Educators Training 2009-2011
-
批准号:8044144
-
项目类别:
-
资助金额:$2.97万
-
财政年份:2009
-
负责人:JOAN M LAKOSKI
-
依托单位:
Clinical Research Scholars and Educators Training 2009-2011
-
批准号:7777822
-
项目类别:
-
资助金额:$3.0万
-
财政年份:2009
-
负责人:JOAN M LAKOSKI
-
依托单位:
GENETIC ANALYSIS OF NEUROTRANSMITTER RECEPTORS IN AGING
-
批准号:6563308
-
项目类别:
-
资助金额:$15.75万
-
财政年份:2002
-
负责人:JOAN M LAKOSKI
-
依托单位:
GENETIC ANALYSIS OF NEUROTRANSMITTER RECEPTORS IN AGING
-
批准号:6631198
-
项目类别:
-
资助金额:$15.75万
-
财政年份:2002
-
负责人:JOAN M LAKOSKI
-
依托单位:
GENETIC ANALYSIS OF NEUROTRANSMITTER RECEPTORS IN AGING
-
批准号:6448898
-
项目类别:
-
资助金额:$15.75万
-
财政年份:2001
-
负责人:JOAN M LAKOSKI
-
依托单位:
CORTICOSTEROID NEUROMODULATION OF SEROTONIN SYSTEM AGING
-
批准号:6349742
-
项目类别:
-
资助金额:$18.99万
-
财政年份:2000
-
负责人:JOAN M LAKOSKI
-
依托单位:
CORTICOSTEROID NEUROMODULATION OF SEROTONIN SYSTEM AGING
-
批准号:6806963
-
项目类别:
-
资助金额:$19.7万
-
财政年份:2000
-
负责人:JOAN M LAKOSKI
-
依托单位:
CORTICOSTEROID NEUROMODULATION OF SEROTONIN SYSTEM AGING
-
批准号:6028102
-
项目类别:
-
资助金额:$19.78万
-
财政年份:2000
-
负责人:JOAN M LAKOSKI
-
依托单位:
CORTICOSTEROID NEUROMODULATION OF SEROTONIN SYSTEM AGING
-
批准号:6761990
-
项目类别:
-
资助金额:$19.19万
-
财政年份:2000
-
负责人:JOAN M LAKOSKI
-
依托单位:
GENETIC ANALYSIS OF NEUROTRANSMITTER RECEPTORS IN AGING
-
批准号:6299396
-
项目类别:
-
资助金额:$17.67万
-
财政年份:2000
-
负责人:JOAN M LAKOSKI
-
依托单位:
CORTICOSTEROID NEUROMODULATION OF SEROTONIN SYSTEM AGING
-
批准号:6497200
-
项目类别:
-
资助金额:$19.56万
-
财政年份:2000
-
负责人:JOAN M LAKOSKI
-
依托单位:
GENETIC ANALYSIS OF NEUROTRANSMITTER RECEPTORS IN AGING
-
批准号:6098766
-
项目类别:
-
资助金额:$17.67万
-
财政年份:1999
-
负责人:JOAN M LAKOSKI
-
依托单位:
AGING AND ESTROGEN ON BIOGENIC AMINE PHYSIOLOGY-RCDA
-
批准号:3070600
-
项目类别:
-
资助金额:$6.81万
-
财政年份:1989
-
负责人:JOAN M LAKOSKI
-
依托单位:
AGING AND ESTROGEN ON BIOGENIC AMINE PHYSIOLOGY-RCDA
-
批准号:3070596
-
项目类别:
-
资助金额:$5.49万
-
财政年份:1989
-
负责人:JOAN M LAKOSKI
-
依托单位:
AGING AND ESTROGEN ON BIOGENIC AMINE PHYSIOLOGY-RCDA
-
批准号:3070599
-
项目类别:
-
资助金额:$5.94万
-
财政年份:1989
-
负责人:JOAN M LAKOSKI
-
依托单位:
AGING AND ESTROGEN ON BIOGENIC AMINE PHYSIOLOGY-RCDA
-
批准号:3070601
-
项目类别:
-
资助金额:$0.74万
-
财政年份:1989
-
负责人:JOAN M LAKOSKI
-
依托单位:
AGING AND ESTROGEN ON BIOGENIC AMINE PHYSIOLOGY-RCDA
-
批准号:3070597
-
项目类别:
-
资助金额:$6.83万
-
财政年份:1989
-
负责人:JOAN M LAKOSKI
-
依托单位:
AGING AND ESTROGEN ON BIOGENIC AMINE PHYSIOLOGY-RCDA
-
批准号:3070598
-
项目类别:
-
资助金额:$6.61万
-
财政年份:1989
-
负责人:JOAN M LAKOSKI
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依托单位:
COCAINE AND SEROTONIN FUNCTION: BEHAVIOR AND PHYSIOLOGY
-
批准号:3209754
-
项目类别:
-
资助金额:$9.29万
-
财政年份:1987
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负责人:JOAN M LAKOSKI
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依托单位:
COCAINE AND SEROTONIN FUNCTION: BEHAVIOR AND PHYSIOLOGY
-
批准号:3209748
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项目类别:
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资助金额:$9.11万
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财政年份:1987
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负责人:JOAN M LAKOSKI
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依托单位:
海外基金