Adult Neurogenesis, Regulation and Potential Function

成人神经发生、调节和潜在功能

• 批准号: 0346227
• 负责人: Miles Orchinik
• 金额: --
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0346227&HistoricalAwards=false
• 关键词: Adult; Neurogenesis; Regulation; Potential; Function

For most of the 20th century, the adult brain was thought to lack the neural plasticity seen in young brains and, particularly, to be incapable of generating new neurons. This perspective is falling from favor, as one of the most exciting areas of biological research is the study of adult neurogenesis - the proliferation and differentiation of neuronal progenitor cells. Researchers have recently suggested that the regulation of neurogenesis in adult humans is important in the physiology or pathophysiology of many processes, including cognition, affect, and aging (to name a few). Such avenues of research are likely to become increasingly prominent in biomedical research, but the significance of naturally occurring neurogenesis in adults of any species remains unknown. While neurogenesis in adult songbird brains appears to support seasonal cycles of song learning and memory, the definitive studies remain elusive. The current studies will take advantage of the relatively simple brain of the bullfrog, Rana catesbeiana, to enhance our knowledge of this complex process. We will combine field studies, primary cell culture, and double-labeling using laser confocal microscopy to investigate the fate of cells born in adult frog brains, attempt to identify regulatory mechanisms, and address the potential significance of adult neurogenesis from the perspective of neuroendocrine cells rather than complex behaviors. Specifc aims are to: 1) Characterize the distribution and extent of cell proliferation and the fate of newly generated cells in adult bullfrog brains; 2) Investigate seasonal and sex differences in cell proliferation and/or cell survival; 3) Characterize the proliferation, differentiation and identity of ependymal progenitors in primary culture; 4) Test the hypothesis that stress hormones alter cell proliferation, differentiation or survival; 5) Test the hypotheses that two neurochemicals that may regulate neurogenesis in mammals, serotonin and brain-derived neurotrophic factor, regulate neurogenesis in amphibians; 6) Begin investigating the potential significance of adult neurogenesis by testing the hypothesis that cell proliferation in the preoptic area and hypothalamus leads to generation of cells with known neuroendocrine functions. All the preliminary data presented in this proposal have been obtained by a group of undergraduate researchers representing diverse ethnic, age and socioeconomic groups, and a major goal of these studies is to continue providing opportunities for undergraduate and graduate student research. More than an opportunity to participate in cutting edge neuroscience, research in adult neurogenesis is intrinsically interesting to scientists and the media, making it a wonderful topic for developing student's critical reasoning skills.

在 20 世纪的大部分时间里，人们认为成人大脑缺乏年轻大脑中所见的神经可塑性，特别是无法产生新的神经元。这种观点正在失宠，因为生物学研究中最令人兴奋的领域之一是研究成体神经发生——神经元祖细胞的增殖和分化。研究人员最近提出，成年人神经发生的调节对于许多过程的生理学或病理生理学都很重要，包括认知、情感和衰老（仅举几例）。这种研究途径可能在生物医学研究中变得越来越重要，但任何物种的成年人自然发生的神经发生的意义仍然未知。虽然成年鸣鸟大脑中的神经发生似乎支持歌曲学习和记忆的季节性周期，但确切的研究仍然难以捉摸。目前的研究将利用牛蛙相对简单的大脑来增强我们对这一复杂过程的了解。我们将结合实地研究、原代细胞培养和使用激光共聚焦显微镜的双标记来研究成年青蛙大脑中出生的细胞的命运，尝试确定调节机制，并从神经内分泌细胞而不是复杂行为的角度解决成体神经发生的潜在意义。具体目标是： 1）表征成年牛蛙大脑中细胞增殖的分布和程度以及新生细胞的命运； 2) 研究细胞增殖和/或细胞存活的季节和性别差异； 3) 表征原代培养物中室管膜祖细胞的增殖、分化和身份； 4) 检验应激激素改变细胞增殖、分化或存活的假设； 5）测试两种可能调节哺乳动物神经发生的神经化学物质，血清素和脑源性神经营养因子，调节两栖动物神经发生的假设； 6) 通过检验视前区和下丘脑的细胞增殖导致具有已知神经内分泌功能的细胞产生的假设，开始研究成体神经发生的潜在意义。该提案中提出的所有初步数据都是由一群代表不同种族、年龄和社会经济群体的本科生研究人员获得的，这些研究的一个主要目标是继续为本科生和研究生的研究提供机会。成人神经发生研究不仅是参与尖端神经科学的机会，而且对科学家和媒体来说本质上很有趣，这使其成为培养学生批判性推理技能的绝佳主题。