News Release

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PHILADELPHIA — 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.

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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 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.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.

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