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Paper on Sleep's Restorative Effects Wins 2014 AAAS Newcomb Cleveland Prize

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 is the winner of the 2014 Newcomb Cleveland Prize of the American Association for the Advancement of Science (AAAS).


Scientists watched dye flow through a mouse brain to determine how sleep clears out the daily buildup of toxins in the tissues.| Courtesy of Nedergaard Lab, University of Rochester Medical Center

The Association's oldest prize, now supported by The Fodor Family Trust, 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.

The 2014 prize-winning paper, "Sleep Drives Metabolite Clearance from the Adult Brain," by Lulu Xie of the University of Rochester Medical Center and colleagues was published in the 18 October 2013 issue of Science.

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 more than 60%, 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 and 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 Maiken Nedergaard, co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center. "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 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."

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 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."


Maiken Nedergaard | Vincent Sullivan

"I am especially excited that this award-winning author team contributed to 'Science in the Classroom'," said 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 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."

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. A ceremony and reception will be held in Room 220C of the San Jose Convention Center on Friday, 13 February at 6:15 p.m.