DOI
https://doi.org/10.25772/RKCA-ZF78
Author ORCID Identifier
https://orcid.org/0000-0003-4674-1181
Defense Date
2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Anatomy & Neurobiology
First Advisor
Gretchen Neigh Ph.D.
Abstract
Americans are experiencing an increased prevalence of social isolation and loneliness. A loss of social buffering can occur through loss of loved ones and grief, decline in community support, or a combination following a bout of grief. The perception of loss and loneliness is a complicated entanglement of human emotions and past experiences, and it can be difficult to quantify these states through self-reporting. However, the physical manifestation and consequences are readily identifiable as a burden on cognitive performance, cardiac health, immune system dysregulation, and an increased risk of mortality. Clinical studies have explored the impact of loss on physical metrics using functional neuroimaging and biomarkers of stress with data implicating the neurobiology of loss as a distinct neuropsychiatric disorder. Disturbance of neural processes suggest loss can be a chronic stress disorder with disruption in synaptic function and homeostasis. Foundational preclinical models of social disruption to enable mechanistic examinations of loneliness-related patterns observed in the clinic are still limited. The use of socially monogamous rodents that exhibit post-separation dysregulation of neuroendocrine mechanisms have provided insights into the neurobiology of loss. However, there is a critical gap between understanding the pathology of loneliness or loss in a mechanistic manner that allows us to construct a therapeutic approach to help patients. The goal of this dissertation is to expand our preclinical understanding of partner loss and social isolation to establish a context for exploring the effects of synaptic dysfunction following social disruption within the socially monogamous Peromyscus californicus (California mouse) species. We demonstrate that synaptic mitochondria respiration is altered following social isolation in female mice, but not males, and both sexes have an intensive neuroinflammation response to a systemic endotoxin challenge. Additionally, we explore the impact of aging on gene expression in California mice. These data are positioned to increase our capabilities to explore the neurobiology of loss from the lens of separation as a species relevant chronic stressor, while providing a framework for designing future studies leveraging the California mouse.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
4-11-2025