Adult Neurogenesis, Regulation and Potential Function

在20世纪的大部分时间里，人们认为成年人的大脑缺乏年轻人大脑的神经可塑性，尤其是不能产生新的神经元。这种观点正逐渐失宠，因为生物学研究中最令人兴奋的领域之一是成人神经发生的研究——神经祖细胞的增殖和分化。研究人员最近提出，成人神经发生的调节在许多过程的生理学或病理生理学中都很重要，包括认知、情感和衰老（仅举几例）。这样的研究途径可能在生物医学研究中变得越来越突出，但在任何物种的成人中自然发生的神经发生的意义仍然未知。虽然成年鸣禽大脑中的神经发生似乎支持歌曲学习和记忆的季节性循环，但最终的研究仍然难以捉摸。目前的研究将利用牛蛙（Rana catesbeiana）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、原代细胞培养和激光共聚焦显微镜双重标记来研究成年青蛙大脑中出生细胞的命运，试图确定调节机制，并从神经内分泌细胞而不是复杂行为的角度来解决成年神经发生的潜在意义。具体目的是：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)表征室管膜祖细胞在原代培养中的增殖、分化和同一性；4)验证应激激素改变细胞增殖、分化或存活的假说；5)验证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)通过测试视前区和下丘脑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，开始研究成人神经发生的潜在意义。本提案中提供的所有初步数据都是由一组代表不同种族、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研究提供机会。成人神经发生的研究不仅仅是一个参与前沿神经科学的机会，对科学家和媒体来说，它本身就是一个有趣的话题，使其成为培养学生批判性推理能力的一个很好的话题。

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.