Neural and hormonal control of visceral systems

内脏系统的神经和激素控制

• 批准号: RGPIN-2014-06253
• 负责人: Lange, Angela
• 金额: $ 3.57万
• 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: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=588899
• 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 how these systems participate in successful behaviours; including aspects of reproduction, digestion, circulation of nutrients and waste, and ecdysis behaviour. We have observed that some neuroactive chemicals are expressed in a variety of cell types and so it is possible that these neuroactive chemicals might in themselves represent functional units that interact to bias the insect towards a new functional state or behaviour. In addition, 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 (CNS), and circulation of haemolymph (blood) and neurohormones. The research objects of the proposed research program lie in the following areas: 1) to define the integrative neuroendocrine control of reproductive structures and associated visceral tissues (eg. digestive, cardiac) in the agricultural pest Locusta migratoria and in the medically-important vector of Chagas’ disease, Rhodnius prolixus; and 2) to define the integrative control of ecdysis behaviour (shedding of the exoskeleton) through the coordinated action of neuropeptides on CNS and associated peripheral systems (cardiac, digestive, skeletal muscle). 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: Our long term goal is to study how cells communicate with one another in order to produce an appropriate physiological and behavioral output. We identify and define the interactions between the diverse neurochemicals which are used in our model systems, and also look at interactions / coordination of organ systems. 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. For example, just like the pharmaceutical industry, the agrochemical industry is targeting neuroactive chemicals and GPCRs for novel pest control strategies due to the ever increasing resistance to the current generation of pesticides. The future is hopeful, especially for neuropeptides, where the intrinsic problems associated with their use have been overcome. This need for control is particularly relevant for our model insects, L. migratoria and R. prolixus. Locusts are agricultural pests, eating or destroying crops and affecting over 20% of the earth’s land and more than 65 of the world’s poorest countries. Their swarms lead to devastating consequences in many developing countries. The medically-important insect, R. prolixus, is the vector of human Chagas disease, and whilst once considered to be confined to the Americas, Chagas disease now occurs throughout the World due to human migration and blood transfusions. For example, it is estimated that 300,000 people are infected in the USA, 50,000 in Spain and 2,000 in Canada. 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、组织和器官系统如何受到神经元和神经内分泌途径的调节和整合，这些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（gpcr）和第二信使。我们感兴趣的是这些系统如何参与成功的行为；包括繁殖、消化、营养物质和废物的循环以及蜕化行为。我们已经观察到，一些神经活性化学物质在各种细胞类型中表达，因此这些神经活性化学物质本身可能代表功能单位，这些功能单位相互作用，使昆虫偏向于新的功能状态或行为。此外，这些神经活性化学物质也是脑肠轴的组成部分，因此作为消化道内分泌/神经系统、神经内分泌系统、中枢神经系统（CNS）以及血淋巴（血液）和神经激素循环之间的纽带。本课题拟开展的研究主要集中在以下几个方面：1)明确生殖结构及相关内脏组织（如生殖器官）的综合神经内分泌调控。农业害虫迁徙蝗（Locusta migratoria）和医学上重要的南美锥虫病（Chagas’disease）病媒长Rhodnius prolixus；2)通过神经肽对中枢神经系统和相关外周系统（心脏、消化、骨骼肌）的协调作用，定义对蜕皮行为（外骨骼脱落）的综合控制。