RUI: Cells from the Immune System Generate Adult-born Neurons in Crayfish

RUI：免疫系统细胞在小龙虾中产生成年神经元

• 批准号: 1456918
• 负责人: Barbara Beltz
• 金额: $ 19.5万
• 依托单位: Wellesley College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1456918&HistoricalAwards=false
• 关键词: RUI; Cells; Immune; System; Generate

Neurons in crayfish brains can be replaced throughout adult life. The brain neurons are formed by a process that begins when an immature cell, or stem cell, divides and then goes through a process of development that converts the stem cell to a mature neuron. Interestingly, the source of the neuron stem cells is not known in the crayfish. The Principal Investigator proposes that cells in the crayfish?s immune system may be the source of the stem cells. This is a novel idea because it requires that adult cells with a very different function (immunity) change into immature cells with the ability to develop into neurons. The researcher has found evidence to support this idea and will carry out studies to confirm her findings and learn how these potential source cells get from the crayfish circulatory system into the brain. The project will provide research training opportunities for female undergraduates and for students from underrepresented groups. Student experiences will be assessed using institutional and curricular surveys. Outreach activities will be carried out at local K-12 schools, for alumni associations, and for senior citizens in the Older, Wiser Lifelong Learning (OWLLS) program to teach neuroscience and explain the value of using invertebrate animal model systems to study lifelong plasticity in the nervous system. The innate immune system of crayfish is composed of two distinct tissues that contain different cell types with characteristic cell cycle times and properties. In vitro and adoptive transfer methods will be used to identify regions involved in producing putative neuronal precursor cells. Crayfish will be injected with bromodeoxyuridine to label cells that are in the cell cycle. Hemolymph containing BrdU-labeled cells will then be extracted from these donor crayfish, and hemocyte types separated using Percoll gradients. Each hemocyte class will then be tested for its attraction to the niche in vitro, as well as injected into live crayfish for long-term studies that will test whether particular immune-derived cell types do transition into neuron progenitors that then develop into neurons. The neuronal phenotype will be confirmed by labeling for appropriate neurotransmitters and tract-tracing to reveal cellular morphology.

小龙虾大脑中的神经元可以在整个成年生活中被替换。 大脑神经元是由一个过程形成的，这个过程开始于一个未成熟的细胞或干细胞分裂，然后经历一个将干细胞转化为成熟神经元的发育过程。 有趣的是，小龙虾中神经元干细胞的来源尚不清楚。 首席研究员提出，小龙虾中的细胞？的免疫系统可能是干细胞的来源。 这是一个新的想法，因为它需要具有非常不同功能（免疫）的成年细胞转变为具有发育成神经元能力的未成熟细胞。 研究人员已经找到了支持这一想法的证据，并将开展研究来证实她的发现，并了解这些潜在的来源细胞如何从小龙虾的循环系统进入大脑。 该项目将为女大学生和代表性不足群体的学生提供研究培训机会。学生的经验将使用机构和课程调查进行评估。将在当地K-12学校，校友会和老年人中开展外展活动，智慧终身学习（OWLLS）计划教授神经科学，并解释使用无脊椎动物模型系统研究神经系统终身可塑性的价值。小龙虾的先天免疫系统由两种不同的组织组成，这两种组织包含具有特征性细胞周期时间和特性的不同细胞类型。将使用体外和过继转移方法来鉴定参与产生推定的神经元前体细胞的区域。 小龙虾将被注射溴脱氧尿苷来标记处于细胞周期中的细胞。 然后从这些供体小龙虾中提取含有BrdU标记细胞的血淋巴，并使用Percoll梯度分离血细胞类型。然后，每种血细胞类别将在体外测试其对小生境的吸引力，并注射到活的小龙虾中进行长期研究，以测试特定的免疫源性细胞类型是否会转变为神经元祖细胞，然后发育为神经元。将通过标记适当的神经递质和追踪以揭示细胞形态来确认神经元表型。