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
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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Clinical Research Scholars and Educators Training 2009-2011
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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:
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资助金额:$18.99万
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财政年份:2000
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负责人:JOAN M LAKOSKI
-
依托单位:
CORTICOSTEROID NEUROMODULATION OF SEROTONIN SYSTEM AGING
-
批准号:6806963
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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
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依托单位:
CORTICOSTEROID NEUROMODULATION OF SEROTONIN SYSTEM AGING
-
批准号:6761990
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项目类别:
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资助金额:$19.19万
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财政年份:2000
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负责人:JOAN M LAKOSKI
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依托单位:
GENETIC ANALYSIS OF NEUROTRANSMITTER RECEPTORS IN AGING
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批准号:6299396
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项目类别:
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资助金额:$17.67万
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财政年份:2000
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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
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负责人:JOAN M LAKOSKI
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依托单位:
GENETIC ANALYSIS OF NEUROTRANSMITTER RECEPTORS IN AGING
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依托单位:
AGING AND ESTROGEN ON BIOGENIC AMINE PHYSIOLOGY-RCDA
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批准号:3070600
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项目类别:
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资助金额:$6.81万
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财政年份:1989
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负责人:JOAN M LAKOSKI
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依托单位:
AGING AND ESTROGEN ON BIOGENIC AMINE PHYSIOLOGY-RCDA
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批准号:3070596
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项目类别:
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资助金额:$5.49万
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负责人:JOAN M LAKOSKI
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依托单位:
AGING AND ESTROGEN ON BIOGENIC AMINE PHYSIOLOGY-RCDA
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AGING AND ESTROGEN ON BIOGENIC AMINE PHYSIOLOGY-RCDA
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AGING AND ESTROGEN ON BIOGENIC AMINE PHYSIOLOGY-RCDA
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负责人:JOAN M LAKOSKI
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