Format

Send to

Choose Destination
J Physiol. 2017 Aug 15;595(16):5415-5424. doi: 10.1113/JP273009. Epub 2017 Feb 22.

A mechanism for sickness sleep: lessons from invertebrates.

Author information

1
Department of Neurology, Centre for Sleep and Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Abstract

During health, animal sleep is regulated by an internal clock and by the duration of prior wakefulness. During sickness, sleep is regulated by cytokines released from either peripheral cells or from cells within the nervous system. These cytokines regulate central nervous system neurons to induce sleep. Recent research in the invertebrates Caenorhabditis elegans and Drosophila melanogaster has led to new insights into the mechanism of sleep during sickness. Sickness is triggered by exposure to environments such as infection, heat, or ultraviolet light irradiation, all of which cause cellular stress. Epidermal growth factor is released from stressed cells and signals to activate central neuroendocrine cell(s). These neuron(s) release neuropeptides including those containing an amidated arginine(R)-phenylalanine(F) motif at their C-termini (RFamide peptides). Importantly, mechanisms regulating sickness sleep are partially distinct from those regulating healthy sleep. We will here review key findings that have elucidated the central neuroendocrine mechanism of sleep during sickness. Adaptive mechanisms employed in the control of sickness sleep may play a role in correcting cellular homeostasis after various insults. We speculate that these mechanisms may play a maladaptive role in human pathological conditions such as in the fatigue and anorexia associated with autoimmune diseases, with major depression, and with unexplained chronic fatigue.

KEYWORDS:

C. elegans; D. melanogaster; cellular stress; cytokines; epidermal growth factor; sickness; sleep

PMID:
28028818
PMCID:
PMC5556163
DOI:
10.1113/JP273009
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center