Inhibitory amine neurotransmission in parasitic nematodes

寄生线虫的抑制性胺神经传递

• 批准号: 311917-2010
• 负责人: Forrester, Sean
• 金额: $ 1.97万
• 依托单位: University of Ontario Institute of Technology
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=526307
• 关键词: Inhibitory; amine; neurotransmission; parasitic; nematodes

Dopamine and serotonin are neurotransmitters that play important roles in the function of the mammalian central nervous system. Primitive organisms such as nematodes also utilize dopamine and serotonin. However, in nematodes, these molecules appear to have different functions and, perhaps more intriguingly, act on unique receptors from the ligand-gated chloride channel family. These channels have been identified in the free-living nematode Caenorhabditis elegans and recently, by our group, in the parasitic nematode Haemonchus contortus. Both C. elegans and H. contortus are genetically related nematode species. However, they exhibit extreme differences in their size, nutrition and overall lifestyle. H. contortus is blood-feeding parasite that infects cattle, sheep and goats world-wide while C. elegans is a bacteria-feeding soil nematode. The long-term goal of our research is to determine how the nervous system of parasitic nematodes may relate specifically to their life-style. This proposal will investigate the function of serotonin- and dopamine-activated chloride channels in the nervous system of the parasitic nematode H. contortus. Our approach is to determine where in the parasite serotonin and dopamine molecules are released and relate this information to the location and function of the channels that bind these molecules. This will provide important information on the overall function of dopamine and serotonin chloride channels in parasitic nematodes and will provide the foundation for a comparison between the function of these channels in parasitic verses free-living nematodes. This will significantly enhance our understanding of parasitism. Furthermore, since these channels appear to be unique to nematodes, they may be identified, in the future, as attractive targets for the next generation of anti-parasitic drugs. This will have important implications for the control of parasites that are important to Canada.

多巴胺和血清素是在哺乳动物中枢神经系统功能中起重要作用的神经递质。像线虫这样的原始生物也利用多巴胺和血清素。然而，在线虫中，这些分子似乎具有不同的功能，也许更有趣的是，它们作用于配体门控氯通道家族的独特受体。这些通道已经在自由生活的秀丽隐杆线虫中被发现，最近，我们的研究小组在扭曲血线虫中也发现了这些通道。秀丽隐杆线虫和弯曲线虫都是遗传相关的线虫物种。然而，它们在体型、营养和整体生活方式上表现出极大的差异。弯螺旋体是一种血液寄生虫，感染全世界的牛、绵羊和山羊，而秀丽隐杆线虫是一种以细菌为食的土壤线虫。我们研究的长期目标是确定寄生线虫的神经系统如何与它们的生活方式具体相关。本研究将探讨5 -羟色胺和多巴胺激活的氯离子通道在线虫神经系统中的作用。我们的方法是确定寄生虫中释放血清素和多巴胺分子的位置，并将这些信息与结合这些分子的通道的位置和功能联系起来。这将为寄生性线虫中多巴胺和5 -羟色胺氯通道的整体功能提供重要信息，并为寄生性线虫和自由线虫中这些通道的功能比较提供基础。这将大大提高我们对寄生的理解。此外，由于这些通道似乎是线虫独有的，它们可能在未来被确定为下一代抗寄生虫药物的有吸引力的靶点。这将对控制对加拿大很重要的寄生虫产生重要影响。