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Author Notes:

Ellen J. Hess Departments of Pharmacology and Neurology, Emory University School of Medicine, 101 Woodruff Circle, WMB 6303, Atlanta, GA 30322, USA. Fax: + 1 404 712 8576. ejhess@emory.edu

We thank Luis E. Soria-Jasso, Cecilia Prudente, Ryan Kuhar, Megan E. Bailey, Meyeon Shin and Molly E. Ogle for technical assistance, Dr. Kerry Ressler for the lentivirus constructs, Dr. Rodney Feddersen for the L7-Sv4 transgenic mice and Dr. David Yue for Cacanla+/− mice.

Subjects:

Research Funding:

This work was supported by United States National Institutes of Health (R01 NS33592, R01 NS40470 and the Emory Core Facilities grant, P30 NS055077), the Dystonia Medical Research Foundation and Tyler's Hope for a Dystonia Cure Foundation.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • Focal dystonia
  • Cerebellum
  • Lentivirus
  • Electrical stimulation
  • Cre recombinase
  • BENIGN PAROXYSMAL TORTICOLLIS
  • EPISODIC ATAXIA TYPE-2
  • CALCIUM-CHANNEL
  • CACNA1A GENE
  • TRANSGENIC MICE
  • BASAL GANGLIA
  • WRITERS CRAMP
  • MUTANT MOUSE
  • RAT
  • MUTATION

Limited regional cerebellar dysfunction induces focal dystonia in mice

Tools:

Journal Title:

Neurobiology of Disease

Volume:

Volume 49, Number 1

Publisher:

, Pages 200-210

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Dystonia is a complex neurological syndrome broadly characterized by involuntary twisting movements and abnormal postures. The anatomical distribution of the motor symptoms varies among dystonic patients and can range from focal, involving an isolated part of the body, to generalized, involving many body parts. Functional imaging studies of both focal and generalized dystonias in humans often implicate the cerebellum suggesting that similar pathological processes may underlie both. To test this, we exploited tools developed in mice to generate animals with gradients of cerebellar dysfunction. By using conditional genetics to regionally limit cerebellar dysfunction, we found that abnormalities restricted to Purkinje cells were sufficient to cause dystonia. In fact, the extent of cerebellar dysfunction determined the extent of abnormal movements. Dysfunction of the entire cerebellum caused abnormal postures of many body parts, resembling generalized dystonia. More limited regions of dysfunction that were created by electrical stimulation or conditional genetic manipulations produced abnormal movements in an isolated body part, resembling focal dystonia. Overall, these results suggest that focal and generalized dystonias may arise through similar mechanisms and therefore may be approached with similar therapeutic strategies.

Copyright information:

© 2012 Elsevier Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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