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dc.contributor.authorPointer, Kelli
dc.contributor.authorBell, Eric L.
dc.contributor.authorDas, Abhirup
dc.contributor.authorCohen, Dena E.
dc.contributor.authorAsara, John M.
dc.contributor.authorKapur, Karen
dc.contributor.authorBergmann, Sven
dc.contributor.authorPreisig, Martin
dc.contributor.authorOtowa, Takeshi
dc.contributor.authorKendler, Kenneth S.
dc.contributor.authorChen, Xiangning
dc.contributor.authorHettema, John M.
dc.contributor.authorvan den Oord, Edwin J.
dc.contributor.authorRubio, Justin P.
dc.contributor.authorLibert, Sergiy V.
dc.contributor.authorGuarente, Leonard Pershing
dc.date.accessioned2014-01-24T14:22:27Z
dc.date.available2014-01-24T14:22:27Z
dc.date.issued2011-12
dc.date.submitted2011-08
dc.identifier.issn00928674
dc.identifier.issn1097-4172
dc.identifier.urihttp://hdl.handle.net/1721.1/84481
dc.description.abstractSIRT1 is a NAD+-dependent deacetylase that governs a number of genetic programs to cope with changes in the nutritional status of cells and organisms. Behavioral responses to food abundance are important for the survival of higher animals. Here we used mice with increased or decreased brain SIRT1 to show that this sirtuin regulates anxiety and exploratory drive by activating transcription of the gene encoding the monoamine oxidase A (MAO-A) to reduce serotonin levels in the brain. Indeed, treating animals with MAO-A inhibitors or selective serotonin reuptake inhibitors (SSRIs) normalized anxiety differences between wild-type and mutant animals. SIRT1 deacetylates the brain-specific helix-loop-helix transcription factor NHLH2 on lysine 49 to increase its activation of the MAO-A promoter. Both common and rare variations in the SIRT1 gene were shown to be associated with risk of anxiety in human population samples. Together these data indicate that SIRT1 mediates levels of anxiety, and this regulation may be adaptive in a changing environment of food availability.en_US
dc.description.sponsorshipLeukemia & Lymphoma Society of America (Fellowship 5089-09)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.)en_US
dc.description.sponsorshipPaul F. Glenn Foundationen_US
dc.description.sponsorshipNational Center for Research Resources (U.S.) (Grant UL1RR031990)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.cell.2011.10.054en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceElsevier Open Archiveen_US
dc.titleSIRT1 Activates MAO-A in the Brain to Mediate Anxiety and Exploratory Driveen_US
dc.typeArticleen_US
dc.identifier.citationLibert, Sergiy, Kelli Pointer, Eric L. Bell, Abhirup Das, Dena E. Cohen, John M. Asara, Karen Kapur, et al. “SIRT1 Activates MAO-A in the Brain to Mediate Anxiety and Exploratory Drive.” Cell 147, no. 7 (December 2011): 1459-1472. Copyright © 2011 Elsevier Inc.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentPaul F. Glenn Center for Biology of Aging Research (Massachusetts Institute of Technology)en_US
dc.contributor.mitauthorLibert, Sergiy V.en_US
dc.contributor.mitauthorPointer, Kellien_US
dc.contributor.mitauthorBell, Eric L.en_US
dc.contributor.mitauthorDas, Abhirupen_US
dc.contributor.mitauthorCohen, Dena E.en_US
dc.contributor.mitauthorGuarente, Leonard Pershingen_US
dc.relation.journalCellen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsLibert, Sergiy; Pointer, Kelli; Bell, Eric L.; Das, Abhirup; Cohen, Dena E.; Asara, John M.; Kapur, Karen; Bergmann, Sven; Preisig, Martin; Otowa, Takeshi; Kendler, Kenneth S.; Chen, Xiangning; Hettema, John M.; van den Oord, Edwin J.; Rubio, Justin P.; Guarente, Leonarden_US
dc.identifier.orcidhttps://orcid.org/0000-0003-4064-2510
mit.licensePUBLISHER_POLICYen_US


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