MICROMAPPING OF LEAD INDUCED CHANGES TO NMDA RECEPTORS
铅引起的 NMDA 受体变化的微图谱
基本信息
- 批准号:6524699
- 负责人:
- 金额:$ 10.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-08-02 至 2004-07-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (Taken from the Candidate's Abstract)
The widespread use of lead has made lead exposure a serious environmental and
occupational hazard. Children are particularly vulnerable to the effects of
lead and exposure can cause serious cognitive and behavioral deficits.
Although lead is a known environmental neurotoxin, the physiological bases of
this toxicity remain unclear. However, evidence suggests that the NMDA-type
glutamate receptor function is down-regulated by lead, and this down
regulation attenuates long-term potentiation (LTP), a cellular correlate of
learning. Recent studies of downregulation have used binding assays and
immunocytochemistry to show that binding of agonist is reduced after lead
treatment. While these studies provide valuable information, they are not
functional assays of receptors in intact tissue. The candidate will determine
how lead modifies NMDA receptor function with a novel, high resolution method
of localizing and characterizing receptor function. This method uses local
photolysis of caged agonists to isolate 3 um membrane sections in living cells
within brain slices. The candidate will combine whole-cell voltage clamp
recordings, local photolysis, and calcium imaging to examine the effect of
NMDA receptor downregulation on long-term potentiation and long-term
depression. She hypothesizes that lead decreases NMDA receptor function by
decreasing expression of functional receptors, changing receptor subunit
composition, and altering calcium permeability, which attenuates LTP and LTD.
These experiments will provide a basis for examination of the downstream
processes initiated by receptor activation.
描述(摘自候选人摘要)
铅的广泛使用已使铅暴露成为一个严重的环境问题,
职业危害 儿童特别容易受到
铅和接触铅会导致严重的认知和行为缺陷。
虽然铅是一种已知的环境神经毒素,但其生理基础
这种毒性仍不清楚。 然而,有证据表明,
谷氨酸受体功能被铅下调,
调节减弱长时程增强(LTP),这是一种与
学习 最近的下调研究使用了结合测定法,
免疫细胞化学显示在铅后激动剂结合减少
治疗 虽然这些研究提供了有价值的信息,但它们不是
完整组织中受体的功能测定。 候选人将决定
铅如何通过一种新的高分辨率方法改变NMDA受体功能
定位和表征受体功能的方法。 此方法使用本地
在活细胞中分离3 μ m膜部分的笼状激动剂的光解
在大脑切片中。 候选人将联合收割机全细胞电压钳
记录,局部光解和钙成像,以检查
NMDA受体下调对长时程增强和长时程
萧条 她假设铅通过以下方式降低NMDA受体功能:
降低功能性受体的表达,改变受体亚单位
组合物,并改变钙渗透性,从而减弱LTP和LTD。
这些实验将为下游的研究提供依据
由受体激活引发的过程。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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DIANA Leslie PETTIT其他文献
DIANA Leslie PETTIT的其他文献
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{{ truncateString('DIANA Leslie PETTIT', 18)}}的其他基金
The Physiology of Extra Synaptic NMDA Receptors
突触外 NMDA 受体的生理学
- 批准号:
7244067 - 财政年份:2006
- 资助金额:
$ 10.66万 - 项目类别:
The Physiology of Extra Synaptic NMDA Receptors
突触外 NMDA 受体的生理学
- 批准号:
7047251 - 财政年份:2006
- 资助金额:
$ 10.66万 - 项目类别:
MICROMAPPING OF LEAD INDUCED CHANGES TO NMDA RECEPTORS
铅引起的 NMDA 受体变化的微图谱
- 批准号:
6658035 - 财政年份:2001
- 资助金额:
$ 10.66万 - 项目类别:
MICROMAPPING OF LEAD INDUCED CHANGES TO NMDA RECEPTORS
铅引起的 NMDA 受体变化的微图谱
- 批准号:
6132592 - 财政年份:2001
- 资助金额:
$ 10.66万 - 项目类别:
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