Peptidergic mediation/modulation of stress response

应激反应的肽能介导/调节

• 批准号: 2595-2009
• 负责人: Merali, Zul
• 金额: $ 2.91万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2009
• 资助国家: 加拿大
• 起止时间: 2009-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=419596
• 关键词: Peptidergic; mediation; modulation; stress; response

The long-term objective of this research program is to better understand how the brain interprets various types of stressors and coordinates internal bodily responses as well as behavioral outputs to cope with the stressors. It is of course clear that adequate responses to stressors serve to protect the organism. Conversely, inadequate responses to stressors are thought to result in bodily damage, either due to failure to protect the body from stressor-elicited deleterious effects and/or mobilization of a cascade of responses that directly harms the body. In this project, rats will be exposed to stressors of various types including: (a) psychological stressors (e.g. exposure of a rat to its predator, the cat or ferret), (b) restraint stress (which has psychological as well as physical attributes), and (c) direct physiological stressors (e.g. exposure to immune-type stressors), and the responses of the rats monitored. We have deliberately selected to study these types of naturalistic stressors, as they are ethologically sound and more likely to yield heuristically and practically useful information. The brain utilizes various chemical signals (neurotransmitters) to communicate not only with the rest of the body but also between different regions of the brain itself. One particular class of such transmitter molecules that seem important in responding to stress are small hormone-like molecules called peptides. We are able to monitor the release of various brain transmitters/peptides, in freely behaving animals - without them being 'aware' of this process. We will also monitor the release of various hormones and assess the level of anxiety/fear in these animals. Indeed, stressor exposure (be it illness-related, psychological or physical) often results in other disorders or diseases, including depression, anxiety disorders and/or cardiovascular diseases. It is hoped that a better understanding of how the brain chemically interprets and reacts to various stressors may shed new light on how to manage or cope with stressors most effectively and how to correct or treat maladaptive stress responses.

这项研究计划的长期目标是更好地了解大脑如何解释各种类型的压力源，并协调内部身体反应和行为输出以应对压力源。当然，很明显，对应激源的适当反应有助于保护有机体。相反，对应激源的反应不足被认为会导致身体损伤，这要么是因为未能保护身体免受应激源引发的有害影响，要么是因为动员了一系列直接伤害身体的反应。在这个项目中，大鼠将暴露在不同类型的压力下，包括：(A)心理压力(例如，老鼠暴露在捕食者、猫或雪貂面前)，(B)束缚压力(具有心理和生理属性)，以及(C)直接生理压力(例如，暴露于免疫型应激源)，以及被监测大鼠的反应。我们特意选择研究这些类型的自然主义压力源，因为它们在行为学上是健全的，更有可能提供启发式和实用的有用信息。大脑利用各种化学信号(神经递质)不仅与身体的其他部分进行交流，而且还在大脑的不同区域之间进行交流。在压力反应中，有一类特殊的递质分子似乎很重要，那就是被称为多肽的类似激素的小分子。我们能够监测自由行为的动物体内各种大脑递质/多肽的释放--而它们并没有意识到这一过程。我们还将监测各种荷尔蒙的释放，并评估这些动物的焦虑/恐惧程度。事实上，应激源暴露(无论是与疾病有关的、心理上的还是身体上的)往往会导致其他障碍或疾病，包括抑郁症、焦虑症和/或心血管疾病。人们希望，对大脑如何在化学上解释和反应各种压力源的更好理解，可能会为如何最有效地管理或应对压力源，以及如何纠正或治疗适应不良的压力反应提供新的线索。