NEUROENDOCRINE/IMMUNE INTERACTIONS: ROLE OF MELATONIN

描述(申请人摘要)：生理适应预期和 恰逢季节的变化。适应失败与以下因素相关 疾病、死亡率和精神功能障碍的发病率增加，包括 季节性情感障碍和抑郁。白天的长度是主要的 调节各种生理适应的环境线索， 预见季节性挑战。初步研究表明，一天的长度 选择性地调节西伯利亚仓鼠的免疫功能，季节性的 控制生理适应的机制的繁殖物种 到白天的长度已经被广泛研究。仓鼠在短时间内(类似于 至冬季)，白细胞、辅助性T细胞和嗜酸性粒细胞数量增加； 自然杀伤细胞杀伤活性和自发性淋巴母细胞生成 也得到了增强。相比之下，免疫细胞功能的其他指标是 减少，包括T细胞依赖抗体的产生以及 粒细胞和单核细胞的吞噬和氧化爆发活性。 由于神经内分泌系统介导了白天长度对 季节性生殖生理学涉及昼夜节律松果体褪黑素 节奏，建议的主要焦点是测试假设，即 松果体褪黑素节律调节光周期的先天和适应性 免疫系统的功能。对这一假设的一种综合方法是基于 在对免疫反应的大小和节奏进行评估后 白天的长度。免疫细胞功能的日常节律可能是 在特定免疫表型变化的推动下，将解决这一问题。要确定 光周期对免疫功能的影响是否取决于褪黑素的节律， 仓鼠将被摘除松果体并进行定时治疗以取代 褪黑素节奏的特定方面。为此制定了措施 季节性动物模型对多种免疫系统指标的高度评价 灵敏和复杂的流式细胞术表型分析方法， 细胞介导的细胞溶解、抗体同型转换和吞噬细胞 功能。光周期对特定免疫系统参数的调节可能 增强抗病能力，促进适应季节性挑战 环境，并提供了基础，以解决治疗价值 这种治疗方法可以选择性地调节其他物种的免疫功能。 昼夜计时和神经免疫相互作用的基础知识 可能导致开发最大限度提高免疫反应性的新方法 或减缓免疫系统功能的恶化，这与 免疫缺陷、自身免疫、睡眠障碍、衰老和季节性 行为障碍。

DESCRIPTION (applicant's abstract): Physiological adaptations anticipate and coincide with changes in season. Failures to adapt are associated with increased incidence of disease, mortality and mental dysfunctions that include seasonal affective disorders and depression. Day length is the primary environmental cue that regulates a variety of physiological adaptations that anticipate seasonal challenges. Preliminary studies indicate that day length selectively regulates immune functions in the Siberian hamster, a seasonal breeding species in which the mechanism that controls physiological adaptations to day length has been extensively studied. Hamsters in short days (analogous to winter) had increased numbers of leukocytes, T helper cells and eosinophils; natural killer cell cytolytic activity and spontaneous lymphoblastogenesis were also enhanced. In contrast, other indices of immune cell functions were reduced, including T cell-dependent antibody production, as well as phagocytosis and oxidative burst activities by granulocytes and monocytes. Since the neuroendocrine system that mediates the influence of day length on seasonal reproductive physiology involves the circadian pineal melatonin rhythm, the major focus of the proposal is to test the hypothesis that the pineal melatonin rhythm mediates photoperiod control of innate and adaptive immune system functions. An integrative approach to this hypothesis is based upon assessment of the magnitude and tempo of immune responses to changes in day length. The possibility that daily rhythms in immune cell functions are driven by changes in specific immunophenotypes will be addressed. To determine whether photoperiod effects on immune functions depend on the melatonin rhythm, hamsters will be pinealectomized and administered timed treatments to replace specific aspects of the melatonin rhythm. Measures were developed for this seasonal animal model to assess multiple immune system indices by highly sensitive and sophisticated flow cytometry methods for phenotyping, cell-mediated cytolysis, antibody isotype switching and phagocytic cell function. Regulation of specific immune system parameters by photoperiod may potentiate disease resistance, promote adaptations to seasonal challenges in the environment, and provide the foundation to address the therapeutic value of such treatments to selectively modulate immune function in other species. Fundamental knowledge of circadian time keeping and neuroimmune interactions may lead to development of novel approaches to maximize immune responsiveness or slow the deterioration of immune system function that is associated with immunodeficiency, autoimmunity, sleep disturbances, aging and seasonality in behavioral disorders.