LEAD INDUCED CHANGES IN GLUTAMATE RECEPTORS & CORTICAL PLASTICITY

铅引起谷氨酸受体的变化

• 批准号: 6271340
• 负责人: M JOHNSTON
• 金额: $ 16.54万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6271340
• 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和代谢性谷氨酸受体已被证明 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。潜在客户互动与 谷氨酸能信号也已被证实，这些效应可能 改变突触连接并在大脑中造成永久性损伤 功能。建议的研究主要集中在使用一口井- 建立了皮质发育的模型，即体感桶，以 检验铅引起谷氨酸受体改变的假设 改变依赖活动的大脑皮层回路的发育。建议数 研究包括：(1)检测低水平铅的影响 暴露对谷氨酸受体时空表达的影响 谷氨酸受体mRNA在皮质桶状野、海马区和 小脑；(2)铅暴露的影响的检查 不同发育时期大鼠脑内谷氨酸受体的表达 桶状野、海马体和小脑；(3)检查 铅暴露对大鼠脑皮质桶形性可塑性改变的影响 去除新生儿胡须。为了实现这个项目的既定目标， 谷氨酸受体的表达将通过这个项目进行评估，谷氨酸 受体的表达将通过免疫组织化学进行评估，受体 放射自显影和原位杂交。该计划的总体目标 该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来测试阶段 为设计合理的干预策略。