From Social Discruption to Neural Compromise: Establishing Markers and Mediators

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和 延长寿命。然而，当这些社会关系丢失或结束时，感知到的 社会孤立和伴随的孤独会导致显著的生理、心理、 和社会后果，损害个人的功能能力并极大地损害他们的 生活质量。尽管人们普遍认为社会纽带有助于健康，但 社会纽带中断转化为精神和身体损害的机制(S) 健康并没有得到充分的重视。对推动社会变革的生物基础的理解 债券，以及失去社会纽带后的负面后遗症，对于发展一种 减少与孤独相关的健康风险的药物干预框架。 与孤独相关的疾病和疾病都与炎症有关。 和新陈代谢紊乱。拟议的研究将确定社会纽带的程度 扰乱涉及社会物种大脑中的炎症和新陈代谢底物。vt.给出 孤独的负面影响不会简单地通过其他人的存在而得到改善 在人类个体中，有必要检查社会保护的潜在机制 纽带，以及当纽带被打破时参与的生物学，以便开发有针对性的干预措施 在优化那些缺乏积极社会支持的人的身体和心理结果方面。这个 这条研究路线的首要假设是，社会参与的神经胶质反应 键断裂会增加神经炎症并损害神经线粒体功能 通过催产素(OT)信号的中断。利用社会和基因上的一夫一妻制 加州小鼠(Permyscus CalforNicus)，我们将确定配对结合的程度 溶解增加了对挑战的神经炎性反应，并在一定程度上 应激相关行为可预测成对粘合的预期炎症反应 解散(目标1)。我们还将测试对键的分解是否会扰乱突触体 线粒体功能(目标2)。最后，我们将确定OT可以在多大程度上改善 对键溶解对神经-神经胶质轴的影响(目标3)。社会经验的影响 对大脑的影响对于理解精神健康障碍的生物驱动因素和 神经退行性疾病，如阿尔茨海默病和相关痴呆症。

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.