Mechanisms of Social Isolation and Environmental Enrichment in an Animal Model

描述(由申请人提供)：这项研究将调查环境治疗(环境浓缩)的效果，以防止抑郁和心脏病背景下的社会孤立带来的负面情绪和心血管后果。抑郁症和心脏病之间存在双向关联，这种关系对于特定脆弱人群尤其重要，例如人口老龄化或缺乏有益社会经验的个人。对社会应激源和孤独感的心理和生理反应在情感性症状和心血管功能障碍的发生中起重要作用。然而，目前对抑郁症和心脏病患者的治疗非常有限。本项目将使用啮齿动物模型，即社会性一夫一妻制的草原田鼠，来研究行为、自主神经对社会应激源(社会隔离)的反应，以及作为治疗这些负面后果的环境丰富的潜在分子机制。来自我们实验室和其他实验室的初步发现表明，环境丰富--包括以无生命物体和体力活动的形式增加来自环境的刺激--对几个中枢神经系统功能有有益的影响，并可以改善情绪反应和与抑郁相关的行为。草原田鼠是一个有价值的模型系统，用于研究对社会经验的反应以及与情绪和心血管功能有关的神经生物学机制。该物种表现出几种独特的社会行为，模仿人类的行为，包括生活在大家庭中并形成持久的社会纽带；还表现出与人类相似的心脏自主调节。利用草原田鼠模型，特定目标1将使用抑郁的行为测试和连续记录包括血压、心率、心率变异性和自主神经平衡在内的心血管变量，以检验环境丰富是治疗社会孤立的行为和心血管后果的有效方法这一假设。具体目标2将使用包括Delta-FosB免疫反应性在内的中枢神经系统基因的测量方法，来调查这一假设，即大脑皮质、边缘和自主神经区域的长期变化是环境丰富对处于社会隔离状态的动物的积极影响的基础。这项研究提出了一种社会环境影响行为、生理和脑功能的新机制，并将促进抑郁症和心血管疾病患者更全面的治疗方法的发展。 公共卫生相关性：抑郁症和心脏病之间的联系是双向的，并受到社会环境的显著影响。目前的研究项目将在动物模型中调查环境治疗的能力，以防止与情绪和心血管功能障碍相关的负面行为、心血管和大脑过程。这项研究将为抑郁症和心脏病患者开发更有效的治疗方法。

DESCRIPTION (provided by applicant): This research will investigate the effects of an environmental treatment (environmental enrichment), for preventing the negative emotional and cardiovascular consequences of social isolation in the context of depression and heart disease. There is a bidirectional association between depression and heart disease, and this relationship is especially important for people with specific vulnerabilities such as aging populations or individuals who lack beneficial social experiences. Psychological and physiological responses to social stressors and isolation play an important role in the development of affective symptoms and cardiovascular dysfunction. However, current treatments for individuals with depression and heart disease are significantly limited. The present project will use a rodent model, the socially monogamous prairie vole, to study behavioral, autonomic responses to a social stressor (social isolation), and potential molecular mechanisms that underlie environmental enrichment as a treatment for these negative consequences. Preliminary findings, from our laboratory and others, indicate that environmental enrichment - involving increased stimulation from the environment in the form of inanimate objects and physical activity - has beneficial effects on several central nervous system functions, and can improve emotional reactivity and behaviors associated with depression. The prairie vole is a valuable model system for studying responsiveness to social experiences and neurobiological mechanisms related to mood and cardiovascular function. This species displays several unique social behaviors that mimic those of humans, including living in extended families and forming enduring social bonds; and also exhibits autonomic regulation of the heart similar to humans. Using the prairie vole model, Specific Aim 1 will employ behavioral tests of depression and continuous recording of cardiovascular variables including blood pressure, heart rate, heart rate variability, and autonomic balance, to test the hypothesis that environmental enrichment is an effective treatment for behavioral and cardiovascular consequences of social isolation. Specific Aim 2 will employ measures of central nervous system genes including delta-FosB immunoreactivity, to investigate the hypothesis that long-term alterations in cortical, limbic, and autonomic brain regions underlie the positive effects of environmental enrichment in animals that are socially isolated. This research proposes a novel mechanism by which the social environment impacts behavior, physiology, and brain function, and will promote the development of more comprehensive treatments for patients with depression and cardiovascular disease. PUBLIC HEALTH RELEVANCE: The association between depression and heart disease is bidirectional, and is significantly influenced by the social environment. The current research project will investigate, in an animal model, the ability of an environmental treatment to protect against negative behavioral, cardiovascular, and brain processes associated with mood and cardiovascular dysfunction. This research will lead to the development of more effective treatments for patients with depression and heart disease.