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.
Highlights
Sleep is restorative, and its dysregulation can have lead to cognitive, metabolic, and immunological consequences that can have deleterious effects upon human health
These findings are in contrast to male mice, where 8 weeks of Chronic Sleep Fragmentation (CSF) leads to body mass gain (Carreras et al, 2015). This sexual difference in body mass regulation in response to CSF needs to be explored further. This is the first study assessing the effects of adrenergic receptor blockade upon inflammatory responses to either Acute Sleep Fragmentation (ASF) or CSF
There was a tissue-dependent response to phentolamine and propranolol, suggesting that both types of adrenergic receptors play a role in regulating inflammatory responses to sleep fragmentation (SF) (Tables 1 and 2)
Summary
Its dysregulation can have lead to cognitive, metabolic, and immunological consequences that can have deleterious effects upon human health. Our laboratory previously showed that SF-induced increases in cytokine gene expression and serum proteins were mitigated by chemical sympathectomy, confirming that inhibition of the SNS reduces inflammatory responses from acute and chronic SF (Mishra et al, 2020). It is unknown how NE is acting on these target tissues to regulate inflammation
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