From Social Discruption to Neural Compromise: Establishing Markers and Mediators

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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.