Abstract
Sleep is a recuperative process, and its dysregulation has cognitive, metabolic, and immunological effects 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 inflammatory responses, which are influenced by the sympathetic nervous system (SNS). However, the underlying molecular mechanisms contributing to SNS regulation of SF-induced inflammation are not fully understood. To assess the effects of the SNS upon inflammatory responses to SF, C57BL/6j female mice were placed in automated SF chambers with horizontally moving bars across the bottom of each cage at specified intervals to disrupt sleep. Mice were first subjected to either control (no bar movement), acute sleep fragmentation (ASF), or chronic sleep fragmentation (CSF) on a 12:12-h light/dark schedule. ASF involved a bar sweep every 120 s for 24 h, whereas CSF involved a bar sweep every 120 s for 12 h (during 12 L; resting period) over a period of 4 weeks. After exposure to these conditions, mice received an intraperitoneal injection of either phentolamine (5 mg/kg BW; an α-adrenergic receptor blocker), propranolol (5 mg/kg BW; a β-adrenergic receptor blocker), or vehicle (saline). Serum corticosterone concentration, brain and peripheral cytokine (IL1β, TNFα, and TGFβ) mRNA expression, and body mass were assessed. ASF and CSF significantly elevated serum corticosterone concentrations as well as cytokine mRNA expression levels compared with controls, and mice subjected to CSF had decreased body mass relative to controls. 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 β-adrenergic receptors contribute to the SNS mediation of inflammatory responses, and adrenergic antagonists may effectively mitigate tissue-specific SF-mediated inflammation.