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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Pani, Giovambattista Leone, Lucia Galeotti, Tommaso Schütz, Günther Fusco, Salvatore Riccio, Antonella Ranieri, Sofia Chiatamone Grassi, Claudio Ripoli, Cristian Toietta, Gabriele Podda, Maria Vittoria Mcburney, Michael W. |
| Description | Author Affiliation: Fusco S ( Laboratory of Cell Signaling, Institute of General Pathology, Universita' Cattolica School of Medicine, 00168 Rome, Italy.); |
| Abstract | Calorie restriction delays brain senescence and prevents neurodegeneration, but critical regulators of these beneficial responses other than the NAD(+)-dependent histone deacetylase Sirtuin-1 (Sirt-1) are unknown. We report that effects of calorie restriction on neuronal plasticity, memory and social behavior are abolished in mice lacking cAMP responsive-element binding (CREB)-1 in the forebrain. Moreover, CREB deficiency drastically reduces the expression of Sirt-1 and the induction of genes relevant to neuronal metabolism and survival in the cortex and hippocampus of dietary-restricted animals. Biochemical studies reveal a complex interplay between CREB and Sirt-1: CREB directly regulates the transcription of the sirtuin in neuronal cells by binding to Sirt-1 chromatin; Sirt-1, in turn, is recruited by CREB to DNA and promotes CREB-dependent expression of target gene peroxisome proliferator-activated receptor-γ coactivator-1 and neuronal NO Synthase. Accordingly, expression of these CREB targets is markedly reduced in the brain of Sirt KO mice that are, like CREB-deficient mice, poorly responsive to calorie restriction. Thus, the above circuitry, modulated by nutrient availability, links energy metabolism with neurotrophin signaling, participates in brain adaptation to nutrient restriction, and is potentially relevant to accelerated brain aging by overnutrition and diabetes. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 2 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Caloric Restriction Cyclic AMP Response Element-Binding Protein Metabolism Gene Expression Regulation Physiology Neurons Prosencephalon Sirtuin 1 Analysis Of Variance Animals Deficiency Long-Term Potentiation Memory Mice Mice, Inbred C57BL Mice, Mutant Strains Neuronal Plasticity Psychomotor Performance Genetics Social Behavior Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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