SEATTLE, Wash.—November 3, 2010—Researchers at the Allen Institute for Brain Science and SRI International have published the most systematic study to date of the effects of sleep deprivation on gene expression in the brain. The findings have implications for improving the understanding and management of the adverse effects of sleep deprivation on brain function.
The study, available in Frontiers in Neuroscience, has created an extensive and detailed map of gene activity, known as gene expression, in the mouse brain across five behavioral conditions including sleeping, waking and sleep deprivation. Activity of approximately 220 genes responding to these conditions was examined in detail, down to the cellular level, throughout the brain. Additionally, seven brain areas were examined by DNA microarray analysis, which reports the expression levels of tens of thousands of genes and allows a genome-wide analysis of the consequences of sleep deprivation.
"Although most people experience occasional sleep deprivation and recognize its impact on their mood and behavior, there is little scientific understanding of how sleep loss actually affects brain function," said Thomas Kilduff, Ph.D., senior director of the Center for Neuroscience at SRI International. "This pioneering study documents how extending wakefulness affects gene expression in specific brain regions and describes a 'molecular anatomical signature' of sleep deprivation. Our findings may contribute to treatments that will help improve sleep quality and reduce problems arising from sleep deprivation."
By comparing which genes were turned on and where in the brain across the different conditions, the researchers discovered that the majority of the neurons in the forebrain were affected in diverse ways by sleep deprivation, painting a dynamic picture of the molecular consequences of sleep deprivation on higher cognitive functions. Affected forebrain regions include the neocortex, amygdala and hippocampus, which mediate cognitive, emotional and memory functions that are impaired by sleep deprivation.
Detailed analysis of 209 brain areas revealed a novel set of genes not previously associated with sleep deprivation, including genes associated with the stress response, cell-cell signaling, and the regulation of other genes. One gene, neurotensin, has been implicated in schizophrenia and is similarly induced by antipsychotic drugs. These genes may provide potential targets for therapeutic intervention to alleviate the effects of sleep deprivation.
"These data illustrate the complex and dynamic relationship between sleep and sleep deprivation, neuroanatomical pathways and gene expression," said Ed Lein, Ph.D., senior director of neuroscience at the Allen Institute for Brain Science and senior author of the study. "The breadth and level of detail provided by these data will be a unique resource for the scientific community, and to that end we have made the data set publicly available online in its entirety."
The resulting open data resource is one of a growing collection of public online resources provided by the Allen Institute, which was founded by philanthropist Paul G. Allen to advance brain research.
Sleep deprivation leads to a range of cognitive, attention and emotional deficits, including irritability and impaired memory, coordination, and concentration. These effects, which can compromise health, performance and safety, are common among those who work extended hours, including military and medical personnel, and others suffering from chronic sleep loss. Sleep deficits have also been linked to the development of some chronic diseases and disorders, including diabetes, depression, obesity and cardiovascular disease.
The control of sleeping and waking and the consequences of sleep deprivation are believed to be associated with gene activity changes in brain regions involved in sleep regulation and higher level functions. Understanding these changes in gene activity is a critical step toward advances in the treatment of sleep disorders and mitigation of the effects of sleep deprivation.
The data in this study are publicly available via the ALLEN Brain Atlas data portal (www.brain-map.org) as the "Sleep Study". This online dataset comprises a substantial collection of data detailing where specific genes are expressed, or "turned on", throughout the mouse brain for five conditions of sleeping and waking. Specifically, it includes searchable image-based gene expression data for approximately 220 sleep-related genes, genome-wide microarray data for seven sleep-associated brain areas, and a 3D viewing tool for visualizing changes in gene expression across different conditions.
This public resource is a unique resource for sleep researchers worldwide and holds promise for accelerating progress toward understanding and effective treatment of sleep disorders.
Citation: C.L. Thompson et al. (2010) Molecular and anatomical signatures of sleep deprivation in the mouse brain. Frontiers in Neuroscience, Vol. 4, Article 165, doi: 10.3389/fnins.2010.00165.
This work was funded by the Department of the Army USAMRAA award W81XWH-06-1-0131 to the Allen Institute for Brain Science and grant RO1 HL59658 to SRI International from the National Heart, Lung, and Blood Institute of the National Institutes of Health.
The U. S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. The content of this release and this work does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred.
About the Allen Institute for Brain Science
Launched in 2003, the Seattle-based Allen Institute for Brain Science is an independent, 501(c)(3) nonprofit medical research organization dedicated to advancing brain research. Started with $100 million in seed money from philanthropist Paul G. Allen, the Institute takes on projects at the leading edge of science—far-reaching projects at the intersection of biology and technology. The resulting data create publicly available resources that fuel discovery for countless other researchers worldwide. The Institute's data and tools are available on the Web at www.alleninstitute.org.
About SRI's Biosciences Division
SRI's Biosciences Division carries out basic research, drug discovery, and drug development, and provides contract (CRO) services. SRI has all of the resources necessary to take R&D from "Idea to IND"®—from initial discovery to the start of human clinical trials—and specializes in cancer, immunology and inflammation, infectious disease, and neuroscience. SRI's product pipeline has yielded marketed drugs, therapeutics currently in clinical trials, and additional programs in earlier stages. In its CRO business, SRI has helped government and commercial clients and partners advance many drugs into patient testing. SRI is also working to create the next generation of technologies in areas such as diagnostics, drug delivery, medical devices, and systems biology.
About SRI International
Silicon Valley-based SRI International is one of the world's leading independent research and technology development organizations. SRI, which was founded by Stanford University as Stanford Research Institute in 1946 and became independent in 1970, has been meeting the strategic needs of clients and partners for more than 60 years. Perhaps best known for its invention of the computer mouse and interactive computing, SRI has also been responsible for major advances in networking and communications, robotics, drug discovery and development, advanced materials, atmospheric research, education research, economic development, national security, and more. The nonprofit institute performs sponsored research and development for government agencies, businesses, and foundations. SRI also licenses its technologies, forms strategic alliances, and creates spin-off companies. . In 2009, SRI's consolidated revenues, including its wholly owned for-profit subsidiary, Sarnoff Corporation, were approximately $470 million. Sarnoff Corporation, a leader in vision, video, and semiconductor innovations, will be fully integrated into SRI effective January 1, 2011.
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