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

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  • Jun Gao

    (Picower Institute for Learning and Memory, Massachusetts Institute of Technology
    Howard Hughes Medical Institute, Massachusetts Institute of Technology
    Model Animal Research Center, MOE Key Laboratory of Model Animal for Disease Study, Nanjing University)

  • Wen-Yuan Wang

    (Picower Institute for Learning and Memory, Massachusetts Institute of Technology
    Howard Hughes Medical Institute, Massachusetts Institute of Technology)

  • Ying-Wei Mao

    (Picower Institute for Learning and Memory, Massachusetts Institute of Technology
    Howard Hughes Medical Institute, Massachusetts Institute of Technology)

  • Johannes Gräff

    (Picower Institute for Learning and Memory, Massachusetts Institute of Technology
    Stanley Center for Psychiatric Research, Broad Institute)

  • Ji-Song Guan

    (Picower Institute for Learning and Memory, Massachusetts Institute of Technology
    Howard Hughes Medical Institute, Massachusetts Institute of Technology)

  • Ling Pan

    (Picower Institute for Learning and Memory, Massachusetts Institute of Technology
    Howard Hughes Medical Institute, Massachusetts Institute of Technology)

  • Gloria Mak

    (Picower Institute for Learning and Memory, Massachusetts Institute of Technology
    Howard Hughes Medical Institute, Massachusetts Institute of Technology)

  • Dohoon Kim

    (Picower Institute for Learning and Memory, Massachusetts Institute of Technology
    Howard Hughes Medical Institute, Massachusetts Institute of Technology
    Present address: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.)

  • Susan C. Su

    (Picower Institute for Learning and Memory, Massachusetts Institute of Technology
    Howard Hughes Medical Institute, Massachusetts Institute of Technology)

  • Li-Huei Tsai

    (Picower Institute for Learning and Memory, Massachusetts Institute of Technology
    Howard Hughes Medical Institute, Massachusetts Institute of Technology
    Stanley Center for Psychiatric Research, Broad Institute)

Abstract

A role for SIRT1 in memory SIRT1 is a deacetylase involved in DNA repair and genomic stability that was originally identified in non-mammalian model systems as a modulator of longevity. Although it was thought to function in normal brain physiology, it was not known whether SIRT1 participates in higher-order brain functions. Gao et al. now demonstrate such a role for SIRT1: its activation enhances synaptic strength and memory formation. These SIRT1-dependent effects are regulated through a post-transcriptional mechanism involving CREB activation and miR-134 production. This interplay between SIRT1 activation, miR-134 levels and synaptic proteins constitutes a previously unrecognized mechanism of plasticity regulation, and suggests that SIRT1 activation may have therapeutic potential in neurodegenerative diseases involving cognitive impairment.

Suggested Citation

  • Jun Gao & Wen-Yuan Wang & Ying-Wei Mao & Johannes Gräff & Ji-Song Guan & Ling Pan & Gloria Mak & Dohoon Kim & Susan C. Su & Li-Huei Tsai, 2010. "A novel pathway regulates memory and plasticity via SIRT1 and miR-134," Nature, Nature, vol. 466(7310), pages 1105-1109, August.
    • Handle: RePEc:nat:nature:v:466:y:2010:i:7310:d:10.1038_nature09271
    DOI: 10.1038/nature09271
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    Cited by:

    1. Kasandra Burgos & Ivana Malenica & Raghu Metpally & Amanda Courtright & Benjamin Rakela & Thomas Beach & Holly Shill & Charles Adler & Marwan Sabbagh & Stephen Villa & Waibhav Tembe & David Craig & Ke, 2014. "Profiles of Extracellular miRNA in Cerebrospinal Fluid and Serum from Patients with Alzheimer's and Parkinson's Diseases Correlate with Disease Status and Features of Pathology," PLOS ONE, Public Library of Science, vol. 9(5), pages 1-20, May.
    2. Shu Liu & Jianbo Xiu & Caiyun Zhu & Kexin Meng & Chen Li & Rongrong Han & Tingfu Du & Lanlan Li & Lingdan Xu & Renjie Liu & Wanwan Zhu & Yan Shen & Qi Xu, 2021. "Fat mass and obesity-associated protein regulates RNA methylation associated with depression-like behavior in mice," Nature Communications, Nature, vol. 12(1), pages 1-13, December.

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