NEUROTRANSMITTER DISORDER IN RETT SYNDROME

RETT 综合征中的神经递质紊乱

• 批准号: 6241064
• 负责人: MICHAEL Van Doren JOHNSTON
• 金额: $ 21.57万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6241064
• 关键词: Rett syndrome; autoradiography; cerebral cortex; cerebral degeneration; corpus striatum; disease /disorder model; dopamine receptor; growth factor; hippocampus; in situ hybridization; laboratory mouse; neuroanatomy; neurons; neurotransmitter metabolism; neurotransmitter receptor; neurotrophic factors; neutralizing antibody; postmortem; prosencephalon

Rett Syndrome (RS) may involve a genetic defect in development of specific groups of neurons in the immature brain. This project will extend studies of the abnormal neurotransmitter circuitry in RS by examining postmortem brain tissue using neurotransmitter receptor autoradiography and by assessing the effects of neuronal degeneration in a rodent model. Following up on neurochemical observations made by Dr. Wenk in the previous grant period (Project 3a), postmortem RS brain, along with age- and sex-matched control brain will be prepared to visualize binding sites for excitatory amino acid receptor subtypes and messenger RNA for these receptors, D1 and D2 dopamine receptors, dopamine reuptake sites, muscarinic receptors and nicotinic receptors. These autoradiographic studies will allow us to assess abnormalities in both the quantity and distribution of receptors for specific groups of neurons that may participate in the neurodegenerative stage of RS. Experiments utilizing a model of neuronal degeneration in dopaminergic and cholinergic projections from the brainstem and diencephalon to the basal ganglia and cerebral cortex in neonatal mice will allow us to interpret the results of analyzing the human tissue. The animal model will also provide information about the effects of injury to these projections on neurons in their terminal fields. Potential therapeutic interventions including supplementation with the growth factors, nerve growth factor (NGF), and brain derived neurotrophic factor (BDNF) will also be tested in the rodent model. The model will also be useful for understanding molecular mechanisms involved in neuronal degeneration and regeneration that may be disrupted in RS.

雷特综合症 (RS) 可能涉及发育过程中的遗传缺陷 未成熟大脑中的特定神经元群。 该项目将 通过以下方式扩展对 RS 异常神经递质回路的研究 使用神经递质受体检查死后脑组织 放射自显影术并通过评估神经元变性的影响 啮齿动物模型。 跟进博士的神经化学观察结果。 Wenk 在上一个资助期（项目 3a），尸检 RS 大脑， 随着年龄和性别匹配的控制大脑将准备好 可视化兴奋性氨基酸受体亚型的结合位点和 这些受体的信使 RNA，D1 和 D2 多巴胺受体，多巴胺 再摄取位点、毒蕈碱受体和烟碱受体。 这些 放射自显影研究将使我们能够评估两个方面的异常情况 特定神经元群的受体的数量和分布 可能参与 RS 的神经退行性阶段。 实验 利用多巴胺能神经元变性模型 从脑干和间脑到基底层的胆碱能投射 新生小鼠的神经节和大脑皮层将使我们能够解释 分析人体组织的结果。 动物模型还将 提供有关伤害对这些预测的影响的信息 其末端区域的神经元。 潜在的治疗干预措施 包括补充生长因子、神经生长因子 （NGF）和脑源性神经营养因子（BDNF）也将被测试 在啮齿动物模型中。 该模型也将有助于理解 神经元变性和再生的分子机制 RS 中可能会受到干扰。