Sympathetic Regulation of Inflammation from Sleep Fragmentation

Western Kentucky University, Bowling Green KY

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Abstract

Primary sleep abnormalities (insomnia, shift work, and obstructive sleep apnea (OSA)) promote an inflammatory environment and are associated with the development of cardiovascular and metabolic disease. However, the mechanisms underlying these relationships are poorly understood. The proposed research examines hormonal and vascular mechanisms that underlie the inflammatory response to sleep loss using genetic and pharmacological approaches in mice. Sleep loss can activate the sympathetic nervous system (SNS) leading to an increase in catecholamines (epinephrine and norepinephrine) as well as elevate blood pressure, but it is unspecified how modulation of these specific components affects inflammatory responses to experimental sleep fragmentation (SF). Aim 1 will examine whether catecholamines play a role in regulating the onset of SF-induced inflammation and the activation of microglia, an important contributor to neuroinflammation. Spefically, mice will receive chemical sympathectomy and then subjected to acute and chronic SF. Pro- and antiinflammatory gene and protein expression will be assessed using RT-PCR and multiplex Luminex protein arrays, respectively. Immunocytochemistry will be used to assess microglia activation. These findings will be validated through pharmacological inhibition of alpha and beta adrenergic receptors. Instead of a classic anti-inflammatory effect, it is predicted that catecholamines will potentiate SF- induced inflammation. Aim 2 will test whether manipulation of blood pressure alters inflammatory responses to vascular sheer stress by comparing the effects of pharmacological blockade of the sympathetic and renin- angiontensin system upon SD-induced inflammation. Taken together, the proposed research will assess the importance of the sympathetic response in mediating inflammation during sleep loss, and provide unique training opportunities for undergraduates interested in conducting biomedical research in endocrinology, cardiovascular physiology, and the neurosciences.