From Social Discruption to Neural Compromise: Establishing Markers and Mediators

从社会扰乱到神经妥协：建立标记和调解者

• 批准号: 10370798
• 负责人: Erica R Glasper
• 金额: $ 62.22万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10370798
• 关键词: Affect; Alzheimer' s disease related dementia; Anxiety; Area; Behavior; Biological; Biology; Brain; Brain region; California; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chronically Ill; Coupled; Data; Depression and Suicide; Disease; Elderly; Emergency department visit; Environmental Risk Factor; Feeling; Health; Health behavior; Heart failure; Hippocampus (Brain); Hormones; Hospitalization; Human; Impairment; Individual; Inflammation; Inflammatory; Inflammatory Response; Intervention; Laboratories; Lead; Life; Link; Loneliness; Longevity; Mediator of activation protein; Medical; Mental Health; Mental disorders; Metabolic; Metabolism; Microglia; Mission; Mitochondria; Modeling; Mus; Nature; Nerve Degeneration; Neurobiology; Neurons; Obesity; Outcome; Oxytocin; Pair Bond; Patients; Peripheral; Peromyscus; Persons; Pharmacology; Physiological; Predisposition; Prefrontal Cortex; Public Health; Quality of life; Reporting; Research; Risk; Risk Factors; Rodent; Role; Signal Transduction; Smoking; Social Behavior; Social Functioning; Social isolation; Social support; Stimulus; Stress; Stroke; Structure; Synapses; Synaptosomes; Testing; Translating; United States; United States National Institutes of Health; Vertebral column; Work; adverse outcome; behavioral response; dementia risk; density; disability; early life stress; experience; experimental study; healthy lifestyle; heart disease risk; improved; mitochondrial dysfunction; mortality risk; neuroinflammation; novel; physical conditioning; physical inactivity; prevent; psychologic; psychological outcomes; relating to nervous system; response; social; social attachment; social influence; social relationships; stressor; transcriptomics

Humans are generally social and these social relationships can promote a healthier lifestyle and increase longevity. Yet, when these social relationships are lost or come to an end, the perceived social isolation and accompanying loneliness can lead to significant physiological, psychological, and social consequences that impair an individual’s ability to function and greatly impairs their quality of life. Although it is widely recognized that social bonds contribute to health, the mechanism(s) by which social bond disruption translates into compromised mental and physical health are not fully appreciated. An understanding of the biological substrates that drive social bonds, and the negative sequelae following loss of social bonds, is essential to develop a framework for pharmacological interventions to reduce health risks associated with loneliness. The conditions and disorders associated with loneliness have each been linked to inflammation and metabolic disruption. The proposed studies will determine the extent to which social bond disruption engages inflammatory and metabolic substrates in the brain of a social species. Given that the negative effects of loneliness are not simply ameliorated by the presence of other individuals in humans, it is essential to examine the underlying protective mechanisms of social bonds, and the biology engaged when bonds are broken, in order to develop interventions aimed at optimizing physical and psychological outcomes for those lacking positive social support. The overarching hypothesis of this line of inquiry is that the neural-glial response engaged by social bond disruption increases neuroinflammation and compromises neural mitochondrial function through disruptions in oxytocin (OT) signaling. Using the socially and genetically monogamous California mouse (Peromyscus californicus), we will determine the extent to which pair bond dissolution increases the neuroinflammatory response to challenge and the extent to which stress-related behaviors can predict the anticipated inflammatory response to pair bond dissolution (Aim 1). We will also test whether pair bond dissolution disrupts synaptosome mitochondrial function (Aim 2). Lastly, we will determine to what extent OT can ameliorate the impact of pair bond dissolution on the neural-glial axis (Aim 3). The impact of social experiences on the brain may be critical to understanding the biological drivers of mental health disorders and neurodegenerative conditions, like Alzheimer’s Disease and related dementias.

人类通常是社会性的，这些社会关系可以促进更健康的生活方式， 增加寿命。然而，当这些社会关系消失或结束时， 社会隔离和伴随的孤独感会导致严重的生理，心理， 和社会后果，损害个人的功能，并大大削弱他们的能力， 生活质量虽然人们普遍认为社会纽带有助于健康， 社会关系破裂转化为身心损害的机制 健康没有得到充分重视。对推动社会发展的生物学基础的理解 社会联系的丧失以及社会联系丧失后的负面后果， 药物干预框架，以减少与孤独相关的健康风险。 与孤独有关的疾病和障碍都与炎症有关 和代谢紊乱拟议中的研究将确定社会纽带在多大程度上 破坏涉及社会物种大脑中的炎症和代谢底物。给定 孤独的负面影响不仅仅是通过他人的存在而得到改善。 在人类个体中，研究社会保护机制的潜在保护机制至关重要。 债券，和生物学从事时，债券被打破，以制定干预措施，目的是 为那些缺乏积极社会支持的人优化身体和心理结果。的 这一系列调查的首要假设是，社会参与的神经胶质反应， 键断裂增加神经炎症并损害神经线粒体功能 通过破坏催产素（OT）信号。利用社会和基因上的一夫一妻制 加州小鼠（Peromyscus californicus），我们将确定在何种程度上对债券 溶解增加了对刺激的神经炎症反应， 压力相关行为可以预测预期的炎症反应， 溶解（目标1）。我们也将测试成对键的分解是否会破坏突触体 线粒体功能（目的2）。最后，我们将确定OT在多大程度上可以改善 对键溶解对神经胶质轴的影响（目标3）。社会经验的影响 对大脑的影响可能对理解心理健康障碍的生物驱动因素至关重要， 神经退行性疾病，如阿尔茨海默病和相关痴呆症。