Brain leptin receptors in inflammation

炎症中的脑瘦素受体

• 批准号: 238546-2006
• 负责人: Luheshi, Giamal
• 金额: $ 2.46万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=361712
• 关键词: Brain; leptin; receptors; inflammation

Communication between the immune system and the brain is important for our ability to respond to and mount an effective defense response against invading pathogens. Products of the peripheral immune system, known as cytokines (eg. Interleukin-1), play an important role in this communication. These molecules can enter the brain from the circulation and can actually be produced by brain cells following a systemic inflammatory or infectious signal. In the brain, cytokines act to trigger a number of 'sickness' responses such as fever, appetite suppression and increased sleep.  We have previously shown that a new member of this family, leptin, which is involved in the physiological control of body weight, stimulates the production of cytokines in the brain and may act as a circulating messenger during disease. Under normal conditions, the main function of leptin is to regulate our appetite, however we have previously demonstrated that in addition to this, it can induce fever, which is a hallmark of disease. More recently we have demonstrated that this effect of leptin is linked to the body's defense mechanisms against bacterial infection and inflammation. These discoveries led us to suggest that the different actions of leptin in the brain ie appetite suppression and fever, are controlled by different brain sites. We now intend to identify these different brain targets and investigate the mechanisms of action of this hormone in disease.

免疫系统和大脑之间的通讯对于我们对入侵病原体做出反应和采取有效防御反应的能力非常重要。外周免疫系统的产物，称为细胞因子（例如白介素-1），在这种通讯中发挥着重要作用。这些分子可以从循环系统进入大脑，实际上可以由脑细胞根据全身炎症或感染信号产生。在大脑中，细胞因子会引发许多“疾病”反应，例如发烧、食欲抑制和睡眠增加。  我们之前已经证明，瘦素是这个家族的新成员，它参与体重的生理控制，刺激大脑中细胞因子的产生，并可能在疾病期间充当循环信使。在正常情况下，瘦素的主要功能是调节我们的食欲，但我们之前已经证明，除此之外，它还会引起发烧，这是疾病的一个标志。最近，我们证明瘦素的这种作用与人体针对细菌感染和炎症的防御机制有关。这些发现使我们认为瘦素在大脑中的不同作用，即食欲抑制和发烧，是由不同的大脑部位控制的。我们现在打算识别这些不同的大脑目标，并研究这种激素在疾病中的作用机制。