Neurobiology of vertebrate reproduction: Neuronal-glial interactions and integrated neuroendocrine regulation at the brain-pituitary interface

脊椎动物繁殖的神经生物学：脑-垂体界面的神经元-胶质细胞相互作用和综合神经内分泌调节

• 批准号: RGPIN-2016-04182
• 负责人: Trudeau, Vance
• 金额: $ 6.63万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=692444
• 关键词: Neurobiology; vertebrate; reproduction; Neuronal; glial

Acquiring new knowledge about how brain hormones and peptides control animal reproduction is the main goal of my research. The long-term objective is to understand how the brain and pituitary gland release hormones that control the ovaries and testes in fish. Environmental signals such as light and temperature can regulate reproduction by changing the levels and activities of key genes and hormones. Moreover, many environmental pollutants can disrupt these fine-tuned processes such that fertility is reduced, or reproduction is totally inhibited. We know this because we have used methods that measure thousands of genes and hundreds of proteins in the brain following hormone treatments or experiments where we alter the environmental conditions. In the last few years my laboratory made two compelling discoveries in the goldfish and zebrafish model organisms that provide the foundation for this proposal. We will specifically study the role of a novel neuropeptide called secretoneurin that we propose to be a new hormone controlling reproduction. Luteinizing hormone is the essential factor controlling egg production or sperm production, and sex steroid production in vertebrate animals, be they fish, frogs or humans. Additionally, we have isolated a special cell type from the brain called the radial glial cell. These cells are similar to stem cells giving rise to neurons in the adult brain. In fish, they are also the estrogen-producing cells in the brain. We will examine the relationship of these cells to neurons, and how this fits into a complex model to understand how the brain regulates reproduction. Our published and preliminary data all indicate that these various functions are similar in fish and mammals. Therefore, the knowledge gained for one model species may help us understand reproduction control mechanisms in other species. On a more practical scale, establishing the factors that regulate luteinizing hormone release may have important applications for controlled reproduction in fish aquaculture. Also very important is that young scientists will conduct this research and get training in state-of-the art techniques. These include methods such as RNA sequencing and bioinformatics, proteomics (a high powered method to measure hundreds of proteins at one time), and genome editing and gene knockout methods for fish. These graduate and undergraduate students and postdoctoral researchers will be mentored on career development and will publish their results in scientific journals. They will be highly sought after by academia, industrial research and development organizations, or government research departments.

获得有关脑激素和肽如何控制动物繁殖的新知识是我研究的主要目标。长期目标是了解大脑和脑垂体如何释放控制鱼类卵巢和睾丸的激素。光和温度等环境信号可以通过改变关键基因和激素的水平和活性来调节生殖。 此外，许多环境污染物会破坏这些微调过程，从而降低生育力，或完全抑制繁殖。我们知道这一点，因为我们使用的方法测量了激素治疗或改变环境条件的实验后大脑中数千个基因和数百个蛋白质。在过去的几年里，我的实验室在金鱼和斑马鱼模式生物中取得了两项引人注目的发现，为这一提议提供了基础。我们将专门研究一种名为分泌神经素的新型神经肽的作用，我们建议它是一种控制生殖的新激素。黄体生成素是控制脊椎动物（无论是鱼、青蛙还是人类）卵子产生或精子产生以及性类固醇产生的重要因素。此外，我们已经从大脑中分离出一种特殊的细胞类型，称为放射状胶质细胞。这些细胞类似于成人大脑中产生神经元的干细胞。 在鱼类中，它们也是大脑中产生雌激素的细胞。我们将研究这些细胞与神经元的关系，以及这如何融入一个复杂的模型，以了解大脑如何调节生殖。我们发表的和初步的数据都表明，这些不同的功能在鱼类和哺乳动物中是相似的。因此，一个模式物种获得的知识可能有助于我们了解其他物种的生殖控制机制。 在一个更实际的规模，建立调节促黄体激素释放的因素可能有重要的应用，在鱼类养殖业的控制繁殖。同样重要的是，年轻的科学家将进行这项研究，并接受最先进技术的培训。这些方法包括RNA测序和生物信息学，蛋白质组学（一种同时测量数百种蛋白质的高性能方法），以及鱼类的基因组编辑和基因敲除方法。这些研究生和本科生以及博士后研究人员将接受职业发展方面的指导，并将在科学期刊上发表他们的成果。它们将受到学术界、工业研究和开发组织或政府研究部门的高度追捧。