SIRT1 Activates MAO-A in the Brain to Mediate Anxiety and Exploratory Drive
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Guarente_SIRT1 activates.pdf
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Author(s)
Pointer, Kelli
Bell, Eric L.
Das, Abhirup
Cohen, Dena E.
Asara, John M.
Kapur, Karen
Bergmann, Sven
Preisig, Martin
Otowa, Takeshi
Kendler, Kenneth S.
Date Issued
December 2011
Journal
Cell
Publisher
Elsevier
Citation
Libert, 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.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Paul F. Glenn Center for Biology of Aging Research (Massachusetts Institute of Technology)
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DOI of Published Version
https://doi.org/10.1016/j.cell.2011.10.054
