Summary: A new study reveals the mechanism behind why we get so sleepy when we’re sick.
Source: University of Pennsylvania.
Penn roundworm study determines what increases sleepiness during illness.
It’s well known that humans and other animals are fatigued and sleepy when sick, but it’s a microscopic roundworm that’s providing an explanation of how that occurs, according to a study from researchers at the Perelman School of Medicine at the University of Pennsylvania. A study published this week in eLife reveals the mechanism for this sleepiness.
Working with a worm’s simple nervous system shows how a single nerve cell named ALA coordinates an organism-wide response to sickness. During sickness, cells are under stress, and organisms experience sleepiness to promote sleep and recover from the cellular stress. In the worm, this sleepiness is caused by release from the ALA neuron of FLP-13 and other neuropeptides, a group of chemicals that send signals between brain neurons.
“Sleep is vitally important in helping both people and animals to recover during sickness,” said senior author David M. Raizen, MD, PhD, an associate professor of Neurology and a member of the Center for Sleep and Circadian Neurobiology. “Similar signaling may operate in humans and other animals to regulate sleep during sickness. These findings create a launching pad towards future research into the mechanisms for illness-induced sleepiness in humans and other organisms.”
These findings reveal that FLP-13 causes sleep by turning down activity in the nervous system cells that help keep an organism awake. Researchers examined genetic mutations to determine which genes cause the worms to fall asleep when FLP-13 is released. This revealed that worms with mutations that cause them to lack a receptor protein called DMSR-1 on cell surfaces do not become sleepy in response to FLP-13. This indicates that DMSR-1 is essential for FLP-13 to trigger sleep.
Next experiments will target whether illness-induced sleepiness in humans and other mammals is triggered via a similar mechanism. If so, this research may be a critical step towards developing drugs to treat human fatigue associated with sickness and other conditions.
Co-authors include first author Michael Iannacone (University of Pennsylvania), Isabel Beets (KU Leuven of Belgium), Lindsey Lopes (University of Pennsylvania), Matthew Churgin (University of Pennsylvania), Christopher Fang-Yen (University of Pennsylvania), Matthew Nelson (Saint Joseph’s University), and Liliane Schoofs (KU Leuven of Belgium).
Funding: Funding was provided by the National Institutes of Health R01NS088432, R21NS091500, and P30ES013508, the European Research Council ERC-2013-ADG-340318, and the Fonds Wetenschappelijk Onderzoek.
Source: Greg Richter – University of Pennsylvania
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “The RFamide receptor DMSR-1 regulates stress-induced sleep in C. elegans” by Michael J Iannacone, Isabel Beets, Lindsey E Lopes, Matthew A Churgin, Christopher Fang-Yen, Matthew D Nelson, Liliane Schoofs, and David M Raizen in eLife. Published online January 17 2017 doi:10.7554/eLife.19837
[cbtabs][cbtab title=”MLA”]University of Pennsylvania “What Causes Sleepiness When Sickness Strikes?.” NeuroscienceNews. NeuroscienceNews, 19 January 2017.
<https://neurosciencenews.com/sickness-sleepiness-5967/>.[/cbtab][cbtab title=”APA”]University of Pennsylvania (2017, January 19). What Causes Sleepiness When Sickness Strikes?. NeuroscienceNew. Retrieved January 19, 2017 from https://neurosciencenews.com/sickness-sleepiness-5967/[/cbtab][cbtab title=”Chicago”]University of Pennsylvania “What Causes Sleepiness When Sickness Strikes?.” https://neurosciencenews.com/sickness-sleepiness-5967/ (accessed January 19, 2017).[/cbtab][/cbtabs]
Abstract
The RFamide receptor DMSR-1 regulates stress-induced sleep in C. elegans
In response to environments that cause cellular stress, animals engage in sleep behavior that facilitates recovery from the stress. In Caenorhabditis elegans, stress-induced sleep(SIS) is regulated by cytokine activation of the ALA neuron, which releases FLP-13 neuropeptides characterized by an amidated arginine-phenylalanine (RFamide) C-terminus motif. By performing an unbiased genetic screen for mutants that impair the somnogenic effects of FLP-13 neuropeptides, we identified the gene dmsr-1, which encodes a G-protein coupled receptor similar to an insect RFamide receptor. DMSR-1 is activated by FLP-13 peptides in cell culture, is required for SIS in vivo, is expressed non-synaptically in several wake-promoting neurons, and likely couples to a Gi/o heterotrimeric G-protein. Our data expand our understanding of how a single neuroendocrine cell coordinates an organism-wide behavioral response, and suggest that similar signaling principles may function in other organisms to regulate sleep during sickness.
“The RFamide receptor DMSR-1 regulates stress-induced sleep in C. elegans” by Michael J Iannacone, Isabel Beets, Lindsey E Lopes, Matthew A Churgin, Christopher Fang-Yen, Matthew D Nelson, Liliane Schoofs, and David M Raizen in eLife. Published online January 17 2017 doi:10.7554/eLife.19837
