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MicroRNA-128 governs neuronal excitability and motor behavior in mice

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  • Chan Lek Tan, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA
  • Joshua L. Plotkin, Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
  • Morten Trillingsgaard Venø, Danmark
  • Melanie von Schimmelmann, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA and Fishberg Department of Neuroscience, Department of Psychiatry, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
  • Philip Feinberg, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA and Fishberg Department of Neuroscience, Department of Psychiatry, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, USA
  • Silas Mann, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA and Fishberg Department of Neuroscience, Department of Psychiatry, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
  • Annie Handler, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA, USA
  • Jørgen Kjems
  • D. James Surmeier, Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
  • Dónal O’Carroll, European Molecular Biology Laboratory, Mouse Biology Unit, Via Ramarini 32, Monterotondo Scalo 00015, Italy and Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, New York, NY 10065, USA
  • Paul Greengard, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA
  • Anne Schaefer, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065, USA and Fishberg Department of Neuroscience, Department of Psychiatry, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
The control of motor behavior in animals and humans requires constant adaptation of neuronal networks to signals of various types and strengths. We found that microRNA-128 (miR-128), which is expressed in adult neurons, regulates motor behavior by modulating neuronal signaling networks and excitability. miR-128 governs motor activity by suppressing the expression of various ion channels and signaling components of the extracellular signal-regulated kinase ERK2 network that regulate neuronal excitability. In mice, a reduction of miR-128 expression in postnatal neurons causes increased motor activity and fatal epilepsy. Overexpression of miR-128 attenuates neuronal responsiveness, suppresses motor activity, and alleviates motor abnormalities associated with Parkinson's-like disease and seizures in mice. These data suggest a therapeutic potential for miR-128 in the treatment of epilepsy and movement disorders.
OriginalsprogEngelsk
TidsskriftScience
Vol/bind342
Nummer6163
Sider (fra-til)1254-1258
Antal sider5
ISSN0036-8075
DOI
StatusUdgivet - 6 dec. 2013

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