Neuroendocrinology

神经内分泌学

• 批准号: CRC-2021-00375
• 负责人: Belsham, Denise
• 金额: $ 10.93万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Canada Research Chairs
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=763265
• 关键词: Neuroendocrinology

Dr. Belsham studies how an intricate system of neurons in the brain controls many of our basic physiological functions, such as feeding, reproduction, and our day-night cycles. These neurons contain specific neuropeptides that distinguish their roles and she has immortalized these neurons to generate "neurons in a dish", which are used globally to study how individual brain cells operate. Her team has discovered that neurons respond to signals with unique signatures and has defined the molecular events that are involved. It is important to understand which signals from the body communicate with the brain to control our normal physiology, but also the role these signals play in disease states with the goal of targeting some of these pathways for therapeutic interventions. These signals include hormones, nutrients, and even industrial chemicals, which in turn regulate the expression of the neuropeptide genes. The Belsham laboratory delineates the molecular events that occur when neurons are activated, the cellular signaling pathways that are necessary to control gene expression, and the resulting changes in gene expression that ultimately lead to neuropeptide release in the brain and/or blood circulation, altering our physiology. For instance, the neuropeptide Y neurons, located in the region of the brain called the hypothalamus, increase feeding and if left uncontrolled can lead to obesity and its associated problems, such as diabetes and heart disease. The neuropeptide Y gene can be detrimentally activated by saturated fat and the endocrine-disrupting chemical bisphenol A. Neuropeptide Y expression is also dependent on the day-night or circadian timing system that is controlled by this same region of the brain. Normal activation of the circadian system results in whole body homeostasis or balance, but if any part of our cellular day-night control system is not working properly, desynchronization of this fine-tuned orchestra may result, leading to disease. This proposal focuses on how these neuropeptide-expressing neurons sense their environment, communicate with each other, and respond with appropriate physiological tasks and how these are altered in disease states. Dr. Belsham's innovative research program has already discovered novel control mechanisms in the brain, and these fundamental studies will provide critical knowledge about the complex nature of integrated neuroendocrine control of basic physiology.

贝尔舍姆博士研究大脑中一个复杂的神经元系统是如何控制我们的许多基本生理功能的，比如进食、繁殖和昼夜循环。这些神经元含有特定的神经肽，这些神经肽可以区分它们的作用，她已经使这些神经元永生，以产生“培养皿中的神经元”，这些神经元在全球范围内用于研究单个脑细胞的运作方式。她的团队发现，神经元对具有独特特征的信号做出反应，并定义了相关的分子事件。重要的是要了解来自身体的哪些信号与大脑沟通以控制我们的正常生理，但也要了解这些信号在疾病状态中所起的作用，目标是针对这些途径进行治疗干预。这些信号包括激素、营养物质，甚至工业化学品，它们反过来调节神经肽基因的表达。贝尔舍姆实验室描述了当神经元被激活时发生的分子事件，控制基因表达所必需的细胞信号通路，以及最终导致大脑和/或血液循环中神经肽释放的基因表达变化，改变我们的生理。例如，位于大脑下丘脑区域的神经肽Y神经元会增加进食，如果不加以控制，可能导致肥胖及其相关问题，如糖尿病和心脏病。神经肽Y基因可以被饱和脂肪和干扰内分泌的化学物质双酚a有害地激活。神经肽Y的表达也依赖于由大脑同一区域控制的昼夜或昼夜节律计时系统。昼夜节律系统的正常激活会导致整个身体的内稳态或平衡，但如果我们细胞昼夜控制系统的任何部分不能正常工作，就可能导致这种微调管弦乐队的不同步，从而导致疾病。本研究的重点是这些表达神经肽的神经元如何感知它们的环境，相互沟通，并响应适当的生理任务，以及这些在疾病状态下是如何改变的。贝尔舍姆博士的创新研究项目已经在大脑中发现了新的控制机制，这些基础研究将为基础生理学综合神经内分泌控制的复杂性提供关键知识。