EXPRESSION OF DEVELOPMENTALLY REGULATED PROTEINS IN HYPOXIA

缺氧条件下发育调控蛋白的表达

• 批准号: 6455820
• 负责人: Susan Hockfield
• 金额: $ 29.31万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6455820
• 关键词: cerebral cortex; cerebral ischemia /hypoxia; cyclins; developmental neurobiology; extracellular matrix proteins; gene expression; glia; hippocampus; histology; intermediate filaments; laboratory rat; monoclonal antibody; myelin basic proteins; neurogenesis; northern blottings; synapsins

Project 3: Expression of developmentally regulated proteins in hypoxia. Chronic hypoxia in the early postnatal period is becoming an increasingly frequent occurrence. The neurodevelopmental consequences of early hypoxia can be severe. If we are to develop strategies to prevent the cognitive and behavioral deficits that result from early postnatal hypoxia, we must first gain a better understanding of the neurobiological consequences of hypoxic insult. In this project we will consider the effects of early hypoxia on the development of the molecular composition of the brain. We will compare normal to hypoxic animals through development and into adulthood to determine if hypoxia induces alterations in the normal time course of expression of several neural proteins and genes. Preliminary studies have shown that the expression of several important developmentally regulated proteins in perturbed by neonatal hypoxia. Abnormal structure/function of the brain as a consequence of insult in the early postnatal period could reflect a delay in normal developmental processes, or a precocious arrest of development. Either of these mechanisms would lead to the abnormalities observed in the hypoxic model used here. The first aim of this project is to determine if periods of early postnatal hypoxia lead to abnormalities in the expression of developmentally regulated neural proteins. The results of these experiments will permit us to distinguish between developmental delay and developmental arrest as potential mechanisms underlying alterations caused by early postnatal hypoxia. "Critical periods" in development, during which the structure and function of neurons can be modified by neuronal activity, have been documented in many areas of the nervous system. Abnormal neuronal activity during these critical periods can lead to irreversible abnormalities in neuronal structure and function. In considering management of infants with early postnatal hypoxia, it is essential to determine if there is a "critical period" during which hypoxia lead to permanent neurological abnormalities. The second aim of this project is to determine if there are "critical periods" for the abnormalities that result from hypoxia. We will establish the time window during which hypoxia produces irreversible changes in neural properties.

项目 3：发育调控蛋白的表达 缺氧。 产后早期慢性缺氧已成为一个问题 越来越频繁地发生。 神经发育后果 早期缺氧可能很严重。 如果我们要制定战略 防止早期认知和行为缺陷 产后缺氧，首先要了解 缺氧损伤的神经生物学后果。 在这个项目中我们 将考虑早期缺氧对发育的影响 大脑的分子组成。 我们将比较正常和缺氧 动物从发育到成年以确定是否缺氧 诱导几种表达的正常时间过程的改变 神经蛋白质和基因。 初步研究表明， 几种重要的发育调节蛋白的表达 新生儿缺氧引起的困扰。 由于损伤而导致大脑结构/功能异常 产后早期可能反映了正常发育的延迟 发育过程，或发育过早停滞。 这些机制中的任何一个都会导致观察到的异常 这里使用的缺氧模型。 该项目的首要目标是 确定产后早期缺氧是否会导致异常 发育调节神经蛋白的表达。 这 这些实验的结果将使我们能够区分 发育迟缓和发育停滞作为潜在机制 产后早期缺氧引起的潜在改变。 发展的“关键时期”，在此期间，结构和 神经元的功能可以通过神经元的活动来改变 记录在神经系统的许多领域。 神经元异常 在这些关键时期的活动可能会导致不可逆转的后果 神经元结构和功能异常。 在考虑 处理产后早期缺氧的婴儿，必须 确定是否存在缺氧导致缺氧的“关键期” 永久性神经系统异常。 该项目的第二个目标 是确定是否存在异常的“关键期” 是缺氧造成的。 我们将在以下期间建立时间窗口 缺氧会导致神经特性发生不可逆的变化。