Document Detail


SIRT1 activates MAO-A in the brain to mediate anxiety and exploratory drive.
MedLine Citation:
PMID:  22169038     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
SIRT1 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.
Authors:
Sergiy Libert; Kelli Pointer; Eric L Bell; Abhirup Das; Dena E Cohen; John M Asara; Karen Kapur; Sven Bergmann; Martin Preisig; Takeshi Otowa; Kenneth S Kendler; Xiangning Chen; John M Hettema; Edwin J van den Oord; Justin P Rubio; Leonard Guarente
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-08
Journal Detail:
Title:  Cell     Volume:  147     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-26     Completed Date:  2012-02-22     Revised Date:  2014-06-27    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1459-72     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Anxiety / genetics*
Behavior, Animal
Brain / metabolism*
Drive
Exploratory Behavior*
Gene Expression Regulation
Humans
Mice
Molecular Sequence Data
Monoamine Oxidase / chemistry,  genetics*
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Sirtuin 1 / genetics*,  metabolism*
Transcription Factors / genetics
Grant Support
ID/Acronym/Agency:
R01 MH040828/MH/NIMH NIH HHS; R01 MH040828-07/MH/NIMH NIH HHS; R01 MH049492/MH/NIMH NIH HHS; R01 MH049492-08/MH/NIMH NIH HHS; R01 MH049492-09/MH/NIMH NIH HHS; R01 MH049492-10/MH/NIMH NIH HHS; R01 MH049492-11/MH/NIMH NIH HHS; R01 MH049492-12/MH/NIMH NIH HHS; UL1 RR031990/RR/NCRR NIH HHS; UL1RR031990/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Transcription Factors; EC 1.4.3.4/Monoamine Oxidase; EC 3.5.1.-/SIRT1 protein, human; EC 3.5.1.-/Sirt1 protein, mouse; EC 3.5.1.-/Sirtuin 1
Comments/Corrections
Comment In:
Cell. 2011 Dec 23;147(7):1436-7   [PMID:  22196720 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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