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Animal models
C08 Motor, cognitive and emotional investigation in a novel rat model of Huntington's disease
  1. Y Abada1,
  2. HP Nguyen2,
  3. R Schreiber1,
  4. B Ellenbroek3
  1. 1EVOTEC AG, Hamburg, Germany
  2. 2Department of Medical Genetics, University of Tuebingen, Tübingen, Germany
  3. 3School of Psychology, Victoria University of Wellington, Wellington, New Zealand

Abstract

Background Huntington's disease (HD) is one of the nine neurodegenerative disorders characterised by unstable Glutamine (CAG) repeats expansion in the causative gene. The hallmark feature in HD is progressive medium spiny neurons degeneration in the striatum. As a result, patients present progressive motor dysfunction, cognitive deficits and emotional disturbances. Early emotional and cognitive deficits precede motor dysfunction in HD patients. To date no disease modifying treatment for HD has been discovered. A BACHD rat model for HD which carries the human full length mutated huntingtin gene (mHtt, 97 polyglutamine) was recently established. Previous studies with HD murine models have focused mainly on motor deficits.

Aim The present aim of this study was to investigate the emergence of motor, emotional and cognitive deficits in BACHD rats.

Methods Motor deficits were assessed with Rotarod and Actimot; emotional disturbances were evaluated in a fear conditioning test, and cognitive deficits were investigated with a Cross-maze.

Results Compared with wild type, transgenic rats showed (1) hypoactivity in a spontaneous locomotor activity test; (2) motor coordination imbalance in a rotarod test; (3) a lower freezing response in a fear conditioning test; and (4) difficulty in reversal learning in a strategy shifting task, indicative of a disruption in striatal-prefrontal pathway activity.

Conclusion BACHD rats recapitulate HD-related motor, cognitive and emotional symptoms observed in patients and we propose that the model may lend itself for the assessment of novel drug treatments for this disorder.

  • Fear conditioning
  • Huntington's disease
  • motor deficits
  • neurodegeneration
  • reversal learning
  • strategy shifting
  • transgenic rats

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