SIRT1 Activates MAO-A in the Brain to Mediate Anxiety and Exploratory Drive.

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State: Public
Version: author
Serval ID
serval:BIB_EE2F3C143CBD
Type
Article: article from journal or magazin.
Collection
Publications
Title
SIRT1 Activates MAO-A in the Brain to Mediate Anxiety and Exploratory Drive.
Journal
Cell
Author(s)
Libert S., Pointer K., Bell E.L., Das A., Cohen D.E., Asara J.M., Kapur K., Bergmann S., Preisig M., Otowa T., Kendler K.S., Chen X., Hettema J.M., van den Oord E.J., Rubio J.P., Guarente L.
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
147
Number
7
Pages
1459-1472
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
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.
Pubmed
Web of science
Open Access
Yes
Create date
06/01/2012 10:11
Last modification date
20/08/2019 17:15
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