Dev Proj 4: Identifying IFN-alpha-Induced Microglial Activation Using...

开发项目 4：使用……识别 IFN-α 诱导的小胶质细胞激活

• 批准号: 7287021
• 负责人: ANDREW H MILLER
• 金额: $ 3.82万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7287021
• 关键词: Adherence; Anxiety; Basal Ganglia; Behavior; Behavioral; Brain; Brain region; Cancer Patient; Cancer Survivor; Cerebellum; Communication; Comorbidity; Data; Development; Exhibits; Fatigue; Human; Immune; Immune system; Impaired cognition; Inflammation; Inflammatory; Interferon-alpha; Ligands; Macaca mulatta; Malignant Neoplasms; Mental Depression; Microglia; Modeling; Morbidity - disease rate; Nature; Neuraxis; Neurosecretory Systems; Numbers; Occupational; PK 11195; Pathway interactions; Patients; Peripheral; Peripheral Nervous System; Pharmaceutical Preparations; Population; Positron-Emission Tomography; Price; Problem behavior; Process; Quality of life; Radio; Site; Sleep disturbances; Symptoms; Synaptic plasticity; Testing; cancer diagnosis; cancer therapy; cell type; chronic depression; cytokine; experience; mortality; neurotransmitter metabolism; novel; psychologic; social

Behavioral co-morbidities including depression, anxiety, irritability, sleep disturbances, fatigue and impaired cognition in patients with cancer are a serious problem. Studies have shown that the majority of cancer patients will experience one or more of these symptoms during treatment, with over a third or more of patients experiencing persisting symptoms after cancer treatment (Ahles et al 2002, Patrick et al 2003, Williams and Dale 2006). Unfortunately, however, more often than not, these symptoms go unrecognized and untreated, and are frequently considered necessary evils of having cancer or having undergone cancer therapy. The lack of appreciation of behavioral comorbidities in cancer patients can come at a high price. Indeed, a number of studies have documented that cancer patients with behavioral problems exhibit poor adherence to treatment, reduced quality of life, and in several instances, increased morbidity and mortality (Dantzer et al 2001, Hopwood and Stephens 2000, Raison and Miller 2003, Stommel et al 2002). Many reasons are given for the paucity of data regarding the nature and treatment of behavioral problems in cancer patients. However, much of the focus to date has been on the psychological and social/occupational impact of carrying a diagnosis of cancer, which makes it "understandable" why someone with cancer might be emotionally distraught. Nevertheless, exciting new developments regarding communication pathways between the immune system and the brain have revolutionized our understanding of how and why patients may develop behavioral problems during cancer and its treatment (Capuron and Miller 2004, Raison et al 2006). There is increasing appreciation that activation of innate immune inflammatory processes and the release of relevant inflammatory cytokines can significantly influence brain function. Indeed, innate immune cytokines can access the brain and have profound effects on neurotransmitter metabolism, neuroendocrine function, synaptic plasticity and behavior. It remains unclear however, whether cytokines released in the periphery influence brain processes through indirect effects on peripheral nervous system pathways or whether peripheral cytokines activate relevant cell types in the brain including microglia, which in turn become an enduring site of inflammation in the central nervous system.

行为共病包括抑郁、焦虑、烦躁、睡眠障碍、疲劳和 癌症患者的认知受损是一个严重的问题。研究表明，大多数 癌症患者在治疗期间会经历一种或多种这些症状，超过三分之一或更多 癌症治疗后出现持续症状的患者（Ahles et al 2002, Patrick et al 2003, 威廉姆斯和戴尔 2006）。然而不幸的是，这些症状往往未被认识到，并且 未经治疗，通常被认为是患有癌症或已经经历过癌症的必然祸害 治疗。对癌症患者的行为合并症缺乏认识可能会付出高昂的代价。 事实上，许多研究表明，有行为问题的癌症患者表现不佳 坚持治疗、生活质量下降，在某些情况下，发病率和死亡率增加 （Dantzer 等人 2001，Hopwood 和 Stephens 2000，Raison 和 Miller 2003，Stommel 等人 2002）。 关于行为的性质和治疗的数据缺乏有很多原因。 癌症患者的问题。然而，迄今为止，大部分关注点都集中在心理和 被诊断患有癌症的社会/职业影响，这使得“可以理解”为什么某人 患有癌症的人可能会情绪激动。尽管如此，令人兴奋的新进展 免疫系统和大脑之间的通讯途径彻底改变了我们对免疫系统的理解 患者在癌症及其治疗期间如何以及为何会出现行为问题（Capuron 和 Miller） 2004 年，Raison 等人，2006 年）。人们越来越认识到先天免疫炎症的激活 过程和相关炎症细胞因子的释放可以显着影响大脑功能。 事实上，先天免疫细胞因子可以进入大脑并对神经递质产生深远的影响 新陈代谢、神经内分泌功能、突触可塑性和行为。但目前尚不清楚，是否 外周释放的细胞因子通过对周围神经的间接影响来影响大脑过程 系统途径或外周细胞因子是否激活大脑中的相关细胞类型，包括小胶质细胞， 这反过来又成为中枢神经系统中持久的炎症部位。