Chemical sympathectomy reduces peripheral inflammatory responses to acute and chronic sleep fragmentation

Ila Mishra, Keelee B. Pullum, Domnique C. Thayer, Erica R. Plummer, Benjamin W. Conkright, Andrew J. Morris, Bruce F. O'Hara, Gregory E. Demas, Noah T. Ashley

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Sleep loss contributes to the development of cardiovascular, metabolic, and neurological disorders by promoting a systemic proinflammatory phenotype. The neuroendocrine-immune mechanisms contributing to such pathologies are poorly understood. The sympathetic nervous system (SNS) regulates immunity and is often activated following sleep disturbances. The aims of this study were to determine 1) the effect of SNS inhibition on inflammatory responses to sleep fragmentation (SF) and 2) whether homeostasis can be restored after 1 wk of recovery sleep. We measured stress responses (norepinephrine and corticosterone), gene expression levels of pro- and anti-inflammatory cytokines in peripheral (heart, liver, and spleen) tissues, and protein levels of cytokines and chemokines in serum of female mice that were subjected to acute SF for 24 h, chronic SF for 8 wk, or 7 days of recovery after chronic SF. In each experiment, SF and control mice were chemically sympathectomized with 6-hydroxydopamine (6-OHDA) or injected with vehicle. Both acute and chronic SF elevated mRNA and protein levels of cytokines in peripheral tissues. Changes in inflammatory responses mirrored stress-axes activation, with increased corticosterone and norepinephrine in SF mice. 6-OHDA treatment significantly alleviated SF-induced inflammation, thus providing evidence of SNS regulation of peripheral inflammation from SF. Effects of chronic SF were more severe than acute SF, and 1 wk of recovery from SF sufficiently alleviated peripheral inflammatory responses but not NE responses.

Original languageEnglish
Pages (from-to)R781-R789
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume318
Issue number4
DOIs
StatePublished - Apr 2020

Bibliographical note

Funding Information:
This research was supported by the National Institute of General Medical Sciences Grant R15-GM-117534 to N. T. Ashley.

Publisher Copyright:
Copyright © 2020 the American Physiological Society

Keywords

  • Cytokines
  • Inflammation
  • Mice
  • Sleep fragmentation
  • Sympathetic nervous system

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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