Neural and hormonal control of visceral systems

内脏系统的神经和激素控制

• 批准号: RGPIN-2019-05775
• 负责人: Lange, Angela
• 金额: $ 4.74万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=738505
• 关键词: Neural; hormonal; control; visceral; systems

Our long-term goals are to study how cells, tissues and organ systems in insects are regulated and integrated by neurons and neuroendocrine pathways that utilize a variety of neuroactive chemicals (neuropeptides and amines), G-protein coupled receptors (GPCRs) and second messengers. We are interested in determining how these systems participate in successful behaviours; including feeding, digestion, circulation of nutrients and waste, growth, and reproduction. We have observed that some neuroactive chemicals are expressed in a variety of cell types and these neuroactive chemicals might represent functional units that interact to bias the insect towards a new functional state or behaviour. These neuroactive chemicals are also components of the brain-gut axis and therefore serve as a link between the endocrine/neural system of the digestive tract, the neuroendocrine system, the central nervous system, and circulation of haemolymph (blood) and neurohormones. The research objects of the proposed research program involve discovery in the medically-important disease vector, Rhodnius prolixus, and lie in the following areas: 1) integrative control of blood-gorging and the storage and delivery of nutrients; 2) integrative control of reproduction in both male and female R. prolixus initiated by a blood meal; 3) identification of physiological effects of these neuroactive chemicals on circulation; and 4) molecular characterization and distribution of the GPCRs and their ligands involved in behaviours. Our scientific approach is holistic and incorporates multi-facetted aspects from gene to behaviour. We define the neural substrates and circuits (including their neuroactive chemicals and receptors) used in the integrative control of these behaviours using a variety of techniques including molecular biology, pharmacology, neurophysiology, physiological assays, peptide isolation, neural mapping and immunohistochemistry. Novelty and expected significance The importance of research into insects lies increasingly in the testing and demonstration of universal principles of neural organization and functioning, while identifying unique features for target of novel pest control strategies. The future is hopeful, especially for neuropeptides, where the intrinsic problems associated with their use have been overcome. In addition, there is some hope using symbiont-mediated RNAi, whereby the symbiont bacterium that lives in the R. prolixus gut can be modified to deliver dsRNA that targets neuropeptide-signalling pathways. This need for control is particularly relevant for our model, R. prolixus; a medically-important insect that is a major vector of human Chagas disease. While once considered to be confined to the Americas, Chagas disease now occurs throughout the World due to human migration and blood transfusions. Therefore, this research as outlined above, has the potential to discover lead compounds that can be developed into bio-pesticides in the future.

我们的长期目标是研究昆虫的细胞、组织和器官系统是如何受到神经元和神经内分泌途径的调节和整合的，这些神经内分泌途径利用各种神经活性化学物质(神经肽和胺)、G蛋白偶联受体(GPCRs)和第二信使。我们感兴趣的是确定这些系统如何参与成功的行为；包括摄食、消化、营养和废物的循环、生长和繁殖。我们观察到，一些神经活性化学物质在各种类型的细胞中表达，这些神经活性化学物质可能代表相互作用的功能单位，使昆虫倾向于一种新的功能状态或行为。这些神经活性化学物质也是脑-肠轴的组成部分，因此在消化道的内分泌/神经系统、神经内分泌系统、中枢神经系统以及血淋巴(血液)和神经激素的循环之间起着联系作用。拟议的研究计划的研究对象包括在医学上重要的疾病媒介罗氏罗非鱼中发现，并位于以下领域：1)对嗜血和营养物质的储存和输送进行综合控制；2)对雄性和雌性多刺罗非鱼的生殖进行综合控制；3)鉴定这些神经活性化学物质对循环的生理影响；以及4)GPCRs及其与行为有关的配体的分子表征和分布。我们的科学方法是整体的，从基因到行为都包含了多方面的内容。我们使用包括分子生物学、药理学、神经生理学、生理分析、肽分离、神经图谱和免疫组织化学在内的多种技术来定义用于对这些行为进行综合控制的神经底物和神经回路(包括它们的神经活性化学物质和受体)。新颖性和预期意义昆虫研究的重要性越来越在于测试和论证神经组织和功能的普遍原理，同时为新的害虫控制策略的目标确定独特的特征。未来是充满希望的，特别是对于神经肽来说，与其使用相关的内在问题已经被克服。此外，利用共生菌介导的RNAi还有一些希望，借此生活在罗非鱼肠道的共生菌可以被改造成递送针对神经肽信号通路的dsRNA。这种对控制的需求与我们的模型R.prolixus特别相关；R.prolixus是一种具有重要医学意义的昆虫，是人类恰加斯病的主要媒介。虽然一度被认为仅限于美洲，但由于人类迁徙和输血，恰加斯病现在在世界各地发生。因此，如上所述的这项研究，有可能发现未来可以开发成生物农药的先导化合物。