SIRT1 Activates MAO-A in the Brain to Mediate Anxiety and Exploratory Drive
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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/84481 https://orcid.org/0000-0003-4064-2510 |
| _version_ | 1826206096093609984 |
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| author | 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. Libert, Sergiy V. Guarente, Leonard Pershing |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology 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. Libert, Sergiy V. Guarente, Leonard Pershing |
| author_sort | Pointer, Kelli |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:24:01Z |
| format | Article |
| id | mit-1721.1/84481 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:24:01Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/844812022-10-01T15:00:47Z SIRT1 Activates MAO-A in the Brain to Mediate Anxiety and Exploratory Drive 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. Libert, Sergiy V. Guarente, Leonard Pershing Massachusetts Institute of Technology. Department of Biology Paul F. Glenn Center for Biology of Aging Research (Massachusetts Institute of Technology) Libert, Sergiy V. Pointer, Kelli Bell, Eric L. Das, Abhirup Cohen, Dena E. Guarente, Leonard Pershing 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. Leukemia & Lymphoma Society of America (Fellowship 5089-09) National Institutes of Health (U.S.) Paul F. Glenn Foundation National Center for Research Resources (U.S.) (Grant UL1RR031990) 2014-01-24T14:22:27Z 2014-01-24T14:22:27Z 2011-12 2011-08 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/84481 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. https://orcid.org/0000-0003-4064-2510 en_US http://dx.doi.org/10.1016/j.cell.2011.10.054 Cell Article 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. application/pdf Elsevier Elsevier Open Archive |
| spellingShingle | 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. Libert, Sergiy V. Guarente, Leonard Pershing SIRT1 Activates MAO-A in the Brain to Mediate Anxiety and Exploratory Drive |
| title | SIRT1 Activates MAO-A in the Brain to Mediate Anxiety and Exploratory Drive |
| title_full | SIRT1 Activates MAO-A in the Brain to Mediate Anxiety and Exploratory Drive |
| title_fullStr | SIRT1 Activates MAO-A in the Brain to Mediate Anxiety and Exploratory Drive |
| title_full_unstemmed | SIRT1 Activates MAO-A in the Brain to Mediate Anxiety and Exploratory Drive |
| title_short | SIRT1 Activates MAO-A in the Brain to Mediate Anxiety and Exploratory Drive |
| title_sort | sirt1 activates mao a in the brain to mediate anxiety and exploratory drive |
| url | http://hdl.handle.net/1721.1/84481 https://orcid.org/0000-0003-4064-2510 |
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