A novel pathway regulates memory and plasticity via SIRT1 and miR-134.

Nature
Jun GaoLi-Huei Tsai

Abstract

The NAD-dependent deacetylase Sir2 was initially identified as a mediator of replicative lifespan in budding yeast and was subsequently shown to modulate longevity in worms and flies. Its mammalian homologue, SIRT1, seems to have evolved complex systemic roles in cardiac function, DNA repair and genomic stability. Recent studies suggest a functional relevance of SIRT1 in normal brain physiology and neurological disorders. However, it is unknown if SIRT1 has a role in higher-order brain functions. We report that SIRT1 modulates synaptic plasticity and memory formation via a microRNA-mediated mechanism. Activation of SIRT1 enhances, whereas its loss-of-function impairs, synaptic plasticity. Surprisingly, these effects were mediated via post-transcriptional regulation of cAMP response binding protein (CREB) expression by a brain-specific microRNA, miR-134. SIRT1 normally functions to limit expression of miR-134 via a repressor complex containing the transcription factor YY1, and unchecked miR-134 expression following SIRT1 deficiency results in the downregulated expression of CREB and brain-derived neurotrophic factor (BDNF), thereby impairing synaptic plasticity. These findings demonstrate a new role for SIRT1 in cognition and a ...Continue Reading

Associated Datasets

References

Jun 24, 1982·Nature·R G MorrisJ O'Keefe
Oct 7, 1994·Cell·D A Frank, M E Greenberg
Dec 1, 1996·Journal of Neurocytology·M E CalhounP R Mouton
Apr 18, 1997·Biochimica Et Biophysica Acta·Y ShiK M Galvin
May 2, 2003·Annals of the New York Academy of Sciences·Michael S Fanselow, Greg D Gale
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Hwei-Ling ChengKatrin F Chua
Mar 12, 2004·Genes & Development·John G Doench, Phillip A Sharp
Sep 29, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nicola J BroadbentRobert E Clark
Jan 20, 2006·Nature·Gerhard M SchrattMichael E Greenberg
Feb 20, 2007·The Journal of Biological Chemistry·Eric van der VeerJ Geoffrey Pickering
Oct 9, 2007·Molecular and Cellular Neurosciences·C ChiaruttiniE Tongiorgi
Jan 16, 2008·Biochimica Et Biophysica Acta·Roberto FioreGerhard Schratt
Jun 19, 2008·Annual Review of Neuroscience·Steven W Flavell, Michael E Greenberg
Jul 30, 2008·Current Opinion in Neurobiology·Natascha Bushati, Stephen M Cohen
Mar 17, 2009·Science·Yasukazu NakahataPaolo Sassone-Corsi
May 28, 2009·Proceedings of the National Academy of Sciences of the United States of America·Daniel P StefankoMarcelo A Wood
Jul 31, 2009·Nature·Toren FinkelRaul Mostoslavsky
Dec 17, 2009·Genes & Development·Dena E CohenLeonard P Guarente

❮ Previous
Next ❯

Citations

Aug 13, 2011·Cellular and Molecular Life Sciences : CMLS·N F M Olde LoohuisA Aschrafi
Feb 5, 2013·Archives of Dermatological Research·Melissa SerravalloNeil I Brody
Jun 19, 2012·Brain Structure & Function·Katelin F HansenKarl Obrietan
Jan 20, 2012·In Vitro Cellular & Developmental Biology. Animal·Xiaoying ZhangZhichun Feng
Mar 12, 2013·Molecular Neurobiology·Xiao-Hong LiSai Zhang
May 15, 2013·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Javier Cortés-MendozaLeonor Pérez-Martínez
Feb 4, 2014·Neuropharmacology·Bechara J Saab, Isabelle M Mansuy
Feb 6, 2014·Neuropharmacology·Andrii Rudenko, Li-Huei Tsai
Aug 25, 2012·Journal of the American Chemical Society·Reisuke BabaKazuya Kikuchi
Aug 4, 2012·Cell Death and Differentiation·M-L VolvertL Nguyen
Apr 12, 2012·Cell Research·Sherry Aw, Stephen M Cohen
May 7, 2013·Nature Cell Biology·Victoria A RafalskiAnne Brunet
Jun 12, 2012·Nature Medicine·Eva M Jimenez-MateosDavid C Henshall
Oct 27, 2010·Nature Neuroscience·Selma Masri, Paolo Sassone-Corsi
Nov 20, 2012·Nature Neuroscience·Luca TiberiPierre Vanderhaeghen
Sep 17, 2013·Nature Neuroscience·Wen-Yuan WangLi-Huei Tsai
May 20, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jeremy J Day, J David Sweatt
Jun 14, 2012·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Iva B Zovkic, J David Sweatt
Jun 2, 2012·Nature Reviews. Drug Discovery·Joseph A BaurRafael de Cabo
Jul 3, 2013·Nature Reviews. Genetics·Kailiang Sun, Eric C Lai
Jun 10, 2011·The New England Journal of Medicine·Leonard Guarente
Dec 23, 2011·Proceedings of the National Academy of Sciences of the United States of America·Salvatore FuscoGiovambattista Pani
Oct 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Sunghee ChaiRichard H Goodman
Jan 31, 2013·Journal of Molecular Cell Biology·Adam P CarrollMurray J Cairns
Oct 12, 2013·Genes & Development·Leonard Guarente
Jan 17, 2013·Learning & Memory·Iva B ZovkicJ David Sweatt
Aug 21, 2012·Learning & Memory·Shunit Gal-Ben-AriKobi Rosenblum
Nov 23, 2011·Pharmacological Reviews·Carles Cantó, Johan Auwerx
Sep 24, 2011·Oxidative Medicine and Cellular Longevity·Ke XuZhao-Feng Jiang
Aug 21, 2012·Circulation Research·Maha Abdellatif
Jun 14, 2012·BMC Genomics·Mao-Jin YaoXiao-Bing Yuan
Mar 8, 2011·Journal of Cell Science·Takashi Nakagawa, Leonard Guarente

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
PCR
ChIP
pull-down

Software Mentioned

SCAN
UN
NIH imaging
it
LSMeta10

Related Concepts

Related Feeds

Anthelmintics (ASM)

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.