1. Neuroscience
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Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum

  1. Marta Maltese
  2. Jennifer Stanic
  3. Annalisa Tassone
  4. Giuseppe Sciamanna
  5. Giulia Ponterio
  6. Valentina Vanni
  7. Giuseppina Martella
  8. Paola Imbriani
  9. Paola Bonsi
  10. Nicola Biagio Mercuri
  11. Fabrizio Gardoni
  12. Antonio Pisani  Is a corresponding author
  1. University of Rome Tor Vergata, Italy
  2. University of Milan, Italy
  3. Fondazione Santa Lucia IRCCS, Italy
Research Article
  • Cited 16
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Cite this article as: eLife 2018;7:e33331 doi: 10.7554/eLife.33331

Abstract

The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, though it is unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses is critically involved in motor memory. In the Tor1a+/Δgag DYT1 dystonia mouse model, long-term potentiation (LTP) appeared prematurely in a critical developmental window in striatal spiny neurons (SPNs), while long-term depression (LTD) was never recorded. Analysis of dendritic spines showed an increase of both spine width and mature mushroom spines in Tor1a+/Δgag neurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation. BDNF regulates AMPAR expression during development. Accordingly, both proBDNF and BDNF levels were significantly higher in Tor1a+/Δgag mice. Consistently, antagonism of BDNF rescued synaptic plasticity deficits and AMPA currents. Our findings demonstrate that early loss of functional and structural synaptic homeostasis represents a unique endophenotypic trait during striatal maturation, promoting the appearance of clinical manifestations in mutation carriers.

Article and author information

Author details

  1. Marta Maltese

    Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
  2. Jennifer Stanic

    Department of Pharmacology, University of Milan, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.
  3. Annalisa Tassone

    Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
  4. Giuseppe Sciamanna

    Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
  5. Giulia Ponterio

    Lab Neurophysiology and Plasticity, Fondazione Santa Lucia IRCCS, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
  6. Valentina Vanni

    Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
  7. Giuseppina Martella

    Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
  8. Paola Imbriani

    Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3373-5073
  9. Paola Bonsi

    Lab Neurophysiology and Plasticity, Fondazione Santa Lucia IRCCS, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5940-9028
  10. Nicola Biagio Mercuri

    Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
  11. Fabrizio Gardoni

    Department of Pharmacology, University of Milan, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.
  12. Antonio Pisani

    Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
    For correspondence
    pisani@uniroma2.it
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8432-594X

Funding

Ministero dell'Istruzione, dell'Università e della Ricerca (PRIN 2010-2011)

  • Antonio Pisani

Ministero dell'Istruzione, dell'Università e della Ricerca (PRIN 2010-2011)

  • Fabrizio Gardoni

Dystonia Medical Research Foundation (2017)

  • Antonio Pisani

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal breeding and handling were performed in accordance with the guidelines for the use of animals in biomedical research provided by the European Union's directives and Italian laws (2010/63EU, D.lgs. 26/2014; 406 86/609/CEE, D.Lgs 116/1992). The experimental procedures were approved by Fondazione Santa Lucia and University Tor Vergata Animal Care and Use Committees and the Italian Ministry of Health (authorization #223/2017-PR).

Reviewing Editor

  1. Christian Rosenmund, Charité-Universitätsmedizin Berlin, Germany

Publication history

  1. Received: November 3, 2017
  2. Accepted: March 2, 2018
  3. Accepted Manuscript published: March 5, 2018 (version 1)
  4. Version of Record published: March 13, 2018 (version 2)

Copyright

© 2018, Maltese et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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