title: Silent information regulator 1 mediates hippocampal plasticity through presenilin1.
abstract: Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase directly implicated in protecting a wide range of organisms against internal and external metabolic insults. However, the identification of SIRT1-specific DNA targets that confer such protection have remained elusive. Using human cells, we show that SIRT1 binds to, and transcriptionally regulates, a gene locus encoding presenilin1 (PSEN1), a protein intrinsically involved in the function of the γ-secretase protein complex. We also demonstrate that rats fed with resveratrol exhibit a significant increase in sirt1 and psen1 expression. Finally, dietary consumption of resveratrol also leads to an enhanced proliferative state of neuronal stem cells in the rat hippocampus. Our findings reveal a strong link between resveratrol-dependent SIRT1 signaling and hippocampal plasticity in the mammalian brain.
authors.affiliation: Department of Neuroscience and Histology, New York College of Osteopathic Medicine of New York Institute of Technology, Old Westbury, NY 11568, USA.
authors.forename: G
authors.initials: G
authors.lastname: Torres
authors.forename: J N
authors.initials: JN
authors.lastname: Dileo
authors.forename: B H
authors.initials: BH
authors.lastname: Hallas
authors.forename: J M
authors.initials: JM
authors.lastname: Horowitz
authors.forename: J R
authors.initials: JR
authors.lastname: Leheste
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D057809:HEK293 Cells; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D053764:Presenilin-1 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D053764:Presenilin-1; D013267:Stilbenes; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol