EXPRESSION OF DEVELOPMENTALLY REGULATED PROTEINS IN HYPOXIA

缺氧条件下发育调控蛋白的表达

• 批准号: 6273913
• 负责人: Susan Hockfield
• 金额: $ 24.54万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6273913
• 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：在发育中受调节的蛋白质的表达 缺氧。 慢性缺氧在产后早期正在成为一个 越来越频繁地发生。 神经发育后果 早期缺氧可能很严重。 如果我们要制定策略 防止早期造成的认知和行为缺陷 产后缺氧，我们首先必须更好地了解 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展的影响 大脑的分子组成。 我们将比较正常 通过发育到成年的动物，以确定缺氧是否存在 引起几个正常表达时间过程的改变 神经蛋白质和基因。 初步研究表明 表达了几种重要的发育调节蛋白 受到新生儿缺氧的扰动。 大脑的异常结构/功能是侮辱的结果 产后早期可能反映正常的延迟 发展过程，或早熟的发展。 这些机制中的任何一种都会导致在 这里使用的缺氧模型。 该项目的第一个目的是 确定产后早期缺氧的期间是否导致异常 在发育调节的神经蛋白的表达中。 这 这些实验的结果将使我们能够区分 发育延迟和发育停滞作为潜在机制 早期产后缺氧引起的基本改变。 发展中的“关键时期”，在此期间结构和结构 神经元的功能可以通过神经元活性来改变， 记录在神经系统的许多区域。 异常神经元 在这些关键时期的活动可能导致不可逆 神经元结构和功能异常。 在考虑 患有早期产后缺氧的婴儿的管理，必须 确定是否存在一个“关键时期”，在此期间缺氧导致 永久神经异常。 该项目的第二个目标 是确定异常是否存在“关键时期” 这是由于缺氧而导致的。 我们将在期间建立时间窗口 缺氧会导致神经特性的不可逆转变化。