Advisor(s) - Committee Chair
Noah T. Ashley (Director), Simran Banga, and Michael E. Smith
Department of Biology
Master of Science
Generally, sleep is viewed as a recuperative process and its dysregulation has
cognitive, metabolic, immunological, and inflammatory implications that are largely deleterious to human health. Epidemiological and empirical studies have suggested that sleep fragmentation (SF) as result of obstructive sleep apnea (OSA) and other sleep abnormalities leads to pronounced systemic inflammatory responses, which are influenced by the sympathetic nervous system (SNS). However, the underlying molecular mechanisms contributing to SNS regulation of SF-induced inflammatory states are not fully understood. To assess the effects of the SNS system, C57BL/6j female mice were placed in automated SF chambers (12L:12D) and subjected to either control conditions, acute sleep fragmentation (ASF), or chronic sleep fragmentation (CSF) and injected with either a pharmacological adrenergic receptor antagonist or saline. ASF comprised of an automated bar sweep every 120sec for 24h (during 12L:12D; both resting and active periods), whereas CSF comprised of one automated bar sweep every 120sec for 12h (during the 12L; resting period) over a period of 4 weeks. Adrenergic blockade was achieved through an intraperitoneal injection of either phentolamine (5mg/kg BW), an α (alpha)-receptor blocker, or propranolol (5mg/kg BW), a β (beta)-receptor blocker. Serum corticosterone concentration, brain and peripheral cytokine (IL-1β, TNFα, and TGFβ) mRNA expression, and body mass were assessed. Both ASF and CSF significantly elevated serum corticosterone concentrations as well as cytokine mRNA expression levels, and mice subjected to CSF experienced a significant decrease in body mass. Mice subjected to CSF and treated with phentolamine or propranolol had a greater propensity for a decrease in cytokine gene expression compared with ASF, but effects were tissue-specific. Taken together, these results suggest that both α- and beta- adrenergic receptors contribute to the SNS mediation of inflammatory responses, and adrenergic antagonists can effectively mitigate inflammation from SF in some tissues.
Biology | Immunology and Infectious Disease | Integrative Biology | Neuroscience and Neurobiology
Wheeler, Nicholas David, "Effects of Alpha- and Beta-Adrenergic Receptor Blockade upon Inflammatory Responses to Acute And Chronic Sleep Fragmentation" (2020). Masters Theses & Specialist Projects. Paper 3209.