CELL BIRTH, MIGRATION, AND DEATH IN THE DENTATE GYRUS

齿状回细胞的诞生、迁移和死亡

• 批准号: 2252163
• 负责人: Elizabeth Gould
• 金额: $ 10.45万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2252163
• 关键词: adrenalectomy; autoradiography; cell death; cell migration; corticosteroids; dentate gyrus; developmental neurobiology; glutamate receptor; hormone regulation /control mechanism; immunocytochemistry; laboratory rat; neural transmission; neurogenesis; receptor binding; stereotaxic techniques

In the majority of mammalian brain regions, neurogenesis, migration and programmed cell death occur during a discrete time period that begins during gestation. In contrast, the dentate gyrus of the rat undergoes neuronal birth, migration and death throughout the postnatal period and well into adulthood. This neural region is an ideal system in which to study these processes in the absence of similar changes occurring in afferent or efferent neuronal populations. Since the dentate gyrus develops predominantly during the postnatal period, it is especially vulnerable to early environmental perturbations that may yield permanent effects on brain function. Identification of the factors that regulate the development of the dentate gyrus may elucidate the predisposing mechanisms underlying psychiatric conditions, such as depression and posttraumatic stress disorder, the etiologies of which are thought to involve early life experiences. Moreover, studying the cues that influence the birth, migration and survival of cells in the dentate gyrus may ultimately lead to an understanding of the factors that produce abnormal hippocampal development, as seen in schizophrenia, and potentially to the ability to reverse such developmental pathology by replacing aberrant neurons. The broad, long-term objectives of this proposal are to characterize neuronal birth, migration and survival in the developing dentate gyrus and to identify and study the factors that control these processes during the postnatal period and enable their occurrence in adulthood. Specifically, these experiments will examine the effects of adrenal steroids, excitatory input and cell death on neurogenesis, migration and cell survival in this system. A series of experiments assessing the effects of adrenalectomy or hormone administration, pharmacologic receptor blockade or stereotaxic lesions of afferent populations on the birth and migration of cells will be performed using in vivo 3H-thymidine autoradiography combined with Nissl staining and immunohistochemistry for neuronal and glial specific markers. These markers will also be used to assess the possibility that neuroblasts can be stimulated to divide by dying cells. In addition, the effects of adrenal hormones on the development of excitatory amino acid receptors and dendritic spines will be examined using autoradiography and single-section Golgi impregnation respectively. Collectively, these studies are designed to provide a thorough characterization of neuronal birth, migration and survival in this unusual brain region in order to understand the cues that permit these developmental processes to occur throughout the life of the animal.

在大多数哺乳动物大脑区域中，神经发生，迁移和 程序性细胞死亡发生在开始的离散时间内 在妊娠期间。 相比之下，大鼠的齿状回经历 整个产后的神经元出生，迁移和死亡， 到成年。 这个神经区域是一个理想的系统 在没有类似变化的情况下研究这些过程 传入或传染性神经元种群。 由于齿状回 在产后期间主要发展，尤其是 容易受到可能产生永久性的早期环境扰动的影响 对脑功能的影响。 识别调节的因素 齿状回的发展可能会阐明易感性 抑郁症和诸如抑郁症和 创伤后应激障碍，其病因被认为是 涉及早期生活经验。 此外，研究线索 影响细胞在齿状回中的出生，迁移和存活 最终可能导致对产生因素的理解 在精神分裂症中可以看出的海马异常发育， 有可能通过 取代异常神经元。 该提议的广泛，长期目标是表征 发育中的齿状回的神经元出生，迁移和生存 并确定和研究控制这些过程的因素 产后时期并使他们在成年期间发生。 具体而言，这些实验将检查肾上腺的影响 类固醇，兴奋性输入和细胞死亡对神经发生，迁移和 该系统中的细胞存活。 一系列评估的实验 肾上腺切除术或激素给药的作用，药理 受体封锁或立体定位病变的传入群体 细胞的出生和迁移将使用体内3H-胸腺定 放射自显影与NISSL染色和免疫组织化学相结合 神经元和神经胶质特异性标记。 这些标记也将用于 评估可以刺激神经细胞以除以除外的可能性 垂死的细胞。 另外，肾上腺激素对 兴奋性氨基酸受体和树突状棘的发育将 使用放射自显影和单一高尔基浸渍进行检查 分别。 总的来说，这些研究旨在提供 神经元出生，迁移和生存的透彻表征 这个不寻常的大脑区域以了解允许的提示 这些发展过程在整个动物的生命中发生。