LEAD INDUCED CHANGES IN GLUTAMATE RECEPTORS & CORTICAL PLASTICITY

铅引起谷氨酸受体的变化

• 批准号: 6584919
• 负责人: M JOHNSTON
• 金额: $ 21.2万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6584919
• 关键词: autoradiography; developmental neurobiology; glutamate receptor; hippocampus; immunocytochemistry; in situ hybridization; laboratory rat; lead poisoning; messenger RNA; molecular pathology; neural plasticity; newborn animals; receptor expression

DESCRIPTION: NMDA and metabotropic glutamate receptors have been shown to play a role in the activity-dependent formation of synaptic circuitry during critical periods of brain development. Lead interactions with glutamatergic signaling also have been demonstrated and these effects may alter synaptic connectivity and produce permanent impairments in the brain function. The proposed studies focus primarily on the use of a well- established model of cortical development, the somatosensory barrels, to test the hypothesis that lead-induced changes in the glutamate receptors alter activity-dependent development of cortical circuitry. The proposed studies consist of (1) examination of the effects of low-level lead exposure on the temporal and spatial expression of glutamate receptor and glutamate receptor mRNA in the cortical barrel field, hippocampus and cerebellum; (2) examination of the effects of lead exposure during different periods of development on glutamate receptor expression in the barrel fields, hippocampus and cerebellum; and (3) examination of the effects of lead exposure on cortical barrel plasticity changes induced by neonatal whisker removal. To achieve the stated aims of this project, glutamate receptor expression will be evaluated by this project, glutamate receptor expression will be evaluated by immunohistochemistry, receptor autoradiography and in the situ hybridization. The overall goal of the project is to provide insight into the impact of lead on activity- dependent processes critical to normal brain development to test the stage for the design for rational intervention strategies.

描述：NMDA和代谢型谷氨酸受体已被证明是 在突触回路的活动依赖性形成中发挥作用 在大脑发育的关键时期。领导与 也已经证明了神经元能信号传导，这些作用可能 改变突触连接并在大脑中产生永久性损伤 功能建议的研究主要集中在使用井- 皮质发育的模型，体感桶， 测试铅诱导谷氨酸受体变化的假设 改变皮层回路的活动依赖性发展。拟议 研究包括（1）检查低水平铅的影响 暴露对谷氨酸受体时空表达的影响， 皮层桶场、海马和海马中的谷氨酸受体mRNA 小脑;（2）检查铅暴露的影响， 不同发育时期对谷氨酸受体表达的影响 桶场，海马和小脑;和（3）检查 铅暴露对大鼠皮层桶形可塑性的影响 新生儿胡须去除。为了实现该项目的既定目标， 谷氨酸受体的表达将评估本项目，谷氨酸 将通过免疫组织化学、受体和免疫组织化学方法评价受体表达。 放射自显影和原位杂交。的总体目标 项目旨在深入了解铅对活动的影响- 对正常大脑发育至关重要的依赖过程， 设计合理的干预策略。