video: This video shows tracer influx in sleep and awake animals. view more
Credit: [Credit: Lulu Xie]
How does sleep induce the brain's restorative effects? An investigation into the flow of fluids in the space between the brain cells and their role in cleansing the brain of neurotoxic waste products won the 2014 Newcomb Cleveland Prize of the American Association for the Advancement of Science (AAAS).
The Association's oldest prize, now supported by The Fodor Family Trust, the Newcomb Cleveland Prize annually recognizes the author or authors of an outstanding paper published in the Research Articles or Reports sections of the journal Science between June and the following May.
A Science paper by Lulu Xie, Hongyi Kang and colleagues will receive the AAAS prize for 2014. The research was originally published by Science on 18 October 2013.
Xie and colleagues show that, during sleep, the brain clears out harmful toxins or waste that build up during the day. To understand why humans need sleep for good health and normal brain function, they used a number of techniques, among them iontophoresis and in-vivo two-photon imaging, to observe the flow of fluids in the brains of sleeping and awake mice. Specifically, they looked at the fluid flowing in the interstitial space--the areas between the cells in the brain.
The researchers concluded that, during the natural sleep state, the space between brain cells increases by over 60 percent, boosting the flow of cerebrospinal fluid that flushes accumulated waste products of brain metabolism such as β-amyloid (a protein that accumulates in the brain while awake and that is implicated in Alzheimer's disease) from brain tissue.
“The brain maintains its own protected ecosystem and, prior to this finding, no one really understood how the brain exports its waste,” said senior author Dr. Maiken Nedergaard, M.D., D.M.Sc., co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center in New York. “Given the fact that essentially all neurodegenerative diseases are associated with the accumulation of cellular waste products, this gap in our knowledge has been a barrier to new therapies. Understanding how to modulate the brain’s ecosystem for removing toxic waste could point to new ways to treat these diseases.”
"Our work shows that the glymphatic system primarily functions while we sleep and may be incompatible with wakefulness, pointing to the necessity of sleep in maintaining a healthy environment in the brain," she added.
"The awarding of the Newcomb-Cleveland Prize marks one of the highlights of the year for Science and the continuation of a tradition that is more than 90 years old," said Marcia McNutt, editor-in-chief of the Science family of journals. "I am particularly thrilled with this year's selection that explains why organisms require sleep: to flush waste products from the brain. The results are both startling and profound, and will likely impact neuroscience research for years to come."
The work with the glymphatic system has enabled other discoveries. "Recently we have shown that the system becomes impaired during brain injury and may thwart attempts to identify blood-based biomarkers for this condition," said Nedergaard. "We have also observed that the system functions less effectively as we age, which may contribute to the increased risk of dementia and other neurological disorders in older adults."
"I am especially excited that this award-winning author team contributed to 'Science in the Classroom'," said Dr. Shirley Malcom, director of the Education and Human Resources Programs (EHR) at AAAS. Science in the Classroom, launched in October 2013 with support from the National Science Foundation, is a collection of annotated research papers and accompanying teaching materials. The freely available site features specially developed learning exercises and Science research articles annotated by student volunteers.
The resource, now ready for use in the classroom, allows educators to share the thought process behind the research with their students. "The researchers have provided an extraordinary "behind the scenes look" at the methods and results of this paper," added Malcom.
"It was a pleasure to work with the authors and Kenton Hokanson, a graduate student at the University of California, San Francisco, to annotate this paper for the Science in the Classroom resource," said Dr. Melissa McCartney, project director of AAAS' EHR. "We already have feedback from faculty and students who have used the annotated paper in an upper-level undergraduate course with great success."
A related Perspective article, "Sleep It Out," by Suzana Herculano-Houzel from the Institute of Biomedical Sciences at the Universidade Federal do Rio de Janeiro, Brazil suggests that this work may be used to better define waste products that accumulate by day in the brain, heightening risk for seizures or migraines.
The paper, "Sleep Drives Metabolite Clearance from the Adult Brain," by Lulu Xie, Hongyi Kang, Qiwu Xu, Michael J. Chen, Yonghong Liao, Meenakshisundaram Thiyagarajan, John O'Donnell, Daniel J. Christensen, Jeffrey J. Iliff, Takahiro Takano, Rashid Deane, and Maiken Nedergaard from the University of Rochester Medical Center; and Charles Nicholson from the Langone Medical Center at New York University can be found online. (Please note that the article is free without charge, but initial registration is required.)
The prize was established in 1923 with funds donated by Newcomb Cleveland of New York City and was originally called the AAAS Thousand Dollar Prize. It is now known as the AAAS Newcomb Cleveland Prize, and its value has been raised to $25,000. The winner also receives a prize plaque, complimentary registration and reimbursement for reasonable travel and hotel expenses to attend the AAAS Annual Meeting. Eligible Science papers include original research data, theory, or synthesis. They should represent a fundamental contribution to basic knowledge, or a technical achievement of far-reaching consequence. Winning nominations also should be a first-time publication of the author's own work.
The 2013-2014 Newcomb Cleveland Prize Selection Committee included Marcia McNutt, the Science Editor-in-Chief as well as Science Senior Editorial Board members Paul Alivisatos of the Lawrence Berkeley National Laboratory, University of California, Berkeley; Michael Turner, Professor of Astronomy and Astrophysics, University of Chicago; Susan Rosenberg, Professor, Departments of Molecular and Human Genetics, Biochemistry and Molecular Biology, and Molecular Virology and Microbiology, Baylor College of Medicine; Ernst Fehr, Chairman of the Department of Economics, Professor of Microeconomics and Experimental Economic Research at the University of Zürich, Switzerland; Andrew Sugden, Science Deputy Editor, Biological Sciences; Valda Vinson, Science Deputy Editor, Biological Sciences; and Barbara Jasny, Science Deputy Editor, Commentary.
The Newcomb Cleveland Prize will be presented at the 181st AAAS Annual Meeting in San Jose, California, which will take place 12-16 February 2015. The awards ceremony and reception will be held in Room 220C at the San Jose Convention Center on Friday, 13 February, from 6:15 p.m. until 7:30 p.m.
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CONTACTS: Mark Michaud can be reached at Mark_Michaud@URMC.Rochester.edu or +1-585-273-4790. For general information on the AAAS Awards ceremony or other background, Senior Communications Officer Kat Zambon of AAAS can be reached at (202) 326-6434 or kzambon@aaas.org.
See also News from the University of Rochester Medical Center with related video at http://www.urmc.rochester.edu/news/story/index.cfm?id=3956.
About AAAS
The American Association for the Advancement of Science (AAAS) is the world's largest general scientific society, and publisher of the journal Science as well as Science Translational Medicine, Science Signaling, and Science Advances, a new digital, open access journal. AAAS was founded in 1848, and includes more than 250 affiliated societies and academies of science, serving 10 million individuals. Science has the largest paid circulation of any peer-reviewed general science journal in the world, with an estimated total readership of 1 million. The nonprofit AAAS is open to all and fulfills its mission to "advance science and serve society" through initiatives in science policy, international programs, science education, and more. For the latest research news, log onto EurekAlert!, http://www.eurekalert.org, the premier science-news Web site, a service of AAAS.
Supported by The Fodor Family Trust
Stephen P.A. Fodor, Ph.D., and his colleagues were awarded the Newcomb Cleveland Prize in 1991 for their landmark publication which first introduced microarray technology to the scientific community. ("Light-directed, spatially addressable parallel chemical synthesis," with co-authors J. Read, M.C. Pirrung, L. Stryer, A.Lu, and D. Solas, Science, 15 February 1991.)
Fodor began supporting the AAAS Newcomb Cleveland Prize in 2003, helping to more than double the prize's monetary value. "Receiving the Newcomb Cleveland Award in 1991 was the first important public acknowledgement of our invention," he says. "Today, the award remains one of our most valued. We are thrilled to support its continued legacy. It is important to recognize and encourage the innovative work of new scientists as their work will become the foundation for future research and discovery."
AAAS is the world's largest general scientific society, dedicated to
"Advancing science * Serving society."