Sleep loss, either induced by
obstructive sleep apnea or other forms of sleep dysfunction, induces an inflammatory response, as commonly measured by increased circulating levels of pro-inflammatory
cytokines. Increased
catecholamines from sympathetic nervous system (SNS) activation regulates this peripheral
inflammation. However, the role that
catecholamines play in mediating
neuroinflammation from sleep perturbations is undescribed. The aims of this study were to determine (i) the effect of peripheral SNS inhibition upon neuroinflammatory responses to
sleep fragmentation (SF) and (ii) whether homeostasis can be restored after 1 week of recovery sleep. We measured gene expression levels of pro- and anti-inflammatory
cytokines and microglial activity in brain (prefrontal cortex, hippocampus and hypothalamus) of female mice that were subjected to acute SF for 24 hours, chronic SF for 8 weeks, or 7 days of recovery after chronic SF. In each experiment, SF and control mice were peripherally sympathectomized with
6-hydroxydopamine (6-OHDA) or injected with vehicle. SF elevated
cytokine mRNA expression in brain and increased microglial density and cell area in some regions. In addition, chronic SF promoted hyper-ramification in resting microglia upon exposure to chronic, but not acute, SF. Effects of chronic SF were more pronounced than acute SF, and 1 week of recovery was not sufficient to alleviate
neuroinflammation. Importantly,
6-OHDA treatment significantly alleviated SF-induced
inflammation and microglial responses. This study provides evidence of SNS regulation of neural
inflammation from SF, suggesting a potential role for
therapeutics that could mitigate neuroinflammatory responses to sleep dysfunction.