Photoperiod, Melatonin, and Sickness Behaviors

描述（由申请人提供）：感染导致适应性疾病反应的快速发作，称为急性期反应，包括生理变化，如发烧，睡眠增加，以及行为变化，如减少食物和水的摄入量，活动，探索和社会互动。这些所谓的“疾病行为”是有组织的适应性策略，通常对宿主的生存至关重要，而不是疾病的非特异性表现。发动免疫反应在能量上是昂贵的。对于许多生活在非热带栖息地的动物来说，每年冬天都会出现可预见的年度能源短缺。在冬季短暂的日子里，食物供应不足往往与低温下的高体温调节需求相吻合。动物进化出了一些特殊的保存能量的适应性，比如抑制繁殖和生长，以提高冬季存活率。免疫功能和对感染的反应也受到可用能量的限制，并可能因外部环境的变化而改变。提出的实验旨在调查疾病行为或免疫细胞运输是否可能受到可用能量或褪黑素信号的其他因素的影响。拟议研究的具体目的是：(1)确定早期免疫激活是否会引起长期的生殖成本。(2)确定褪黑素是否介导了疾病反应的短时变化。(3)探索褪黑素是否直接作用于淋巴细胞，改变细胞因子的产生。(4)确定短日照和褪黑素是否通过影响脑内环氧化酶（COX）和白细胞介素(IL)-1a水平来缩短发烧持续时间。(5)确定光周期和褪黑激素是否影响免疫细胞群和白细胞运输。(6)确定光周期是否影响应激损害免疫功能的程度。综上所述，这些研究可能会揭示褪黑素治疗发烧和厌食症的新用途。

DESCRIPTION (provided by applicant): Infection results in the rapid onset of adaptive sickness responses, termed the acute phase response, and includes physiological changes such as fever, increased sleep, as well as behavioral changes such as reduced food and water intake, activity, exploration, and social interactions. These so-called "sickness behaviors" are organized, adaptive strategies that are often crucial for host survival, rather than nonspecific manifestations of illness. Mounting an immune response is energetically costly. For many animals living in non-tropical habitats, a predictable annual energy shortage occurs each winter. During the short days of winter, low food availability often coincides with high thermoregulatory demands in low temperatures. Specific adaptations to conserve energy, such as inhibiting reproduction and growth, have evolved among animals to enhance winter survival. Immune function and responses to infection are also constrained by available energy, and may be altered by changes in the external environment. The proposed experiments are designed to investigate whether sickness behaviors or immune cell trafficking may be influenced by available energy or other factors signaled by melatonin. The specific aims of the proposed research are: (1) To determine if early immune activation evokes long-term reproductive costs. (2) To determine if short-day alterations in sickness responses are mediated by melatonin. (3) To discover if melatonin acts directly on lymphocytes to alter cytokine production. (4) To determine if short days and melatonin reduce the duration of fever by affecting brain levels of cyclooxygenase (COX) and interleukin(IL)-1a. (5) To determine if photoperiod and melatonin affect immune cell populations and leukocyte trafficking. (6) To determine if photoperiod influences the extent to which stress compromises immune function. Taken together, these studies may reveal novel therapeutic uses of melatonin on fever and anorexia.