title: A CREB-Sirt1-Hes1 Circuitry Mediates Neural Stem Cell Response to Glucose Availability.
abstract: Adult neurogenesis plays increasingly recognized roles in brain homeostasis and repair and is profoundly affected by energy balance and nutrients. We found that the expression of Hes-1 (hairy and enhancer of split 1) is modulated in neural stem and progenitor cells (NSCs) by extracellular glucose through the coordinated action of CREB (cyclic AMP responsive element binding protein) and Sirt-1 (Sirtuin 1), two cellular nutrient sensors. Excess glucose reduced CREB-activated Hes-1 expression and results in impaired cell proliferation. CREB-deficient NSCs expanded poorly in vitro and did not respond to glucose availability. Elevated glucose also promoted Sirt-1-dependent repression of the Hes-1 promoter. Conversely, in low glucose, CREB replaced Sirt-1 on the chromatin associated with the Hes-1 promoter enhancing Hes-1 expression and cell proliferation. Thus, the glucose-regulated antagonism between CREB and Sirt-1 for Hes-1 transcription participates in the metabolic regulation of neurogenesis.
authors.affiliation: Institute of Human Physiology, Università Cattolica Medical School, 00168 Rome, Italy; San Raffaele Pisana Scientific Institute for Research, Hospitalization and Health Care, 00163 Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Fusco
authors.affiliation: Institute of Human Physiology, Università Cattolica Medical School, 00168 Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Leone
authors.affiliation: Institute of Human Physiology, Università Cattolica Medical School, 00168 Rome, Italy.
authors.forename: Saviana Antonella
authors.initials: SA
authors.lastname: Barbati
authors.affiliation: Institute of General Pathology, Università Cattolica Medical School, 00168 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Samengo
authors.affiliation: Institute of Human Physiology, Università Cattolica Medical School, 00168 Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Piacentini
authors.affiliation: Institute of Physics, Università Cattolica Medical School, 00168 Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maulucci
authors.affiliation: Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Toietta
authors.affiliation: Institute of Human Physiology, Università Cattolica Medical School, 00168 Rome, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Spinelli
authors.affiliation: Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON 81H KL6, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: McBurney
authors.affiliation: Institute of General Pathology, Università Cattolica Medical School, 00168 Rome, Italy. Electronic address: gpani@rm.unicatt.it.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Pani
authors.affiliation: Institute of Human Physiology, Università Cattolica Medical School, 00168 Rome, Italy; San Raffaele Pisana Scientific Institute for Research, Hospitalization and Health Care, 00163 Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Grassi
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D031204:Caloric Restriction; D000066673:Cell Self Renewal / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D051379:Mice; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism*; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000242:Cyclic AMP; D017362:Cyclic AMP Response Element-Binding Protein; D005947:Glucose; D018398:Homeodomain Proteins; D008239:Lysine; D011494:Protein Kinases; D056564:Sirtuin 1; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse
keywords: CREB; Sirt-1; adult neurogenesis; diabetes; metabolism; neural stem cells; nutrients