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Early cognitive dysfunction in the HD 51 CAG transgenic rat model of Huntington's disease

Kyle D Fink1, Julien Rossignol, Andrew T Crane

  • 1Program in Neuroscience, Central Michigan University, USA.

Behavioral Neuroscience
|May 31, 2012
PubMed

Insights

Huntington's disease (HD) transgenic rats show early cognitive deficits before motor symptoms appear. The Spatial Operant Reversal Test (SORT) effectively detects this preclinical cognitive dysfunction in HD models.

Area of Science:

  • Neuroscience
  • Genetics
  • Animal Models

Background:

  • Huntington's disease (HD) is a neurodegenerative disorder characterized by choreic movements and cognitive deficits.
  • The HD transgenic rat (tgHD) model with a 51 CAG repeat exhibits motor deficits starting at 12 months.
  • Preclinical cognitive dysfunction in tgHD rats remains largely uncharacterized.

Purpose of the Study:

  • To investigate whether cognitive dysfunction precedes motor deficits in tgHD rats.
  • To assess the utility of the Spatial Operant Reversal Test (SORT) for detecting early cognitive changes in HD models.

Main Methods:

  • 9-month-old tgHD rats and wild-type (WT) littermates were tested using the SORT paradigm.
  • Spontaneous motor activity was assessed.
  • Morphological and histological brain examinations were performed post-testing.

Main Results:

  • tgHD rats made significantly more errors in reversal learning phases (Phase 2 and 3) of the SORT compared to WT rats.
  • No memory, motor, or motivational deficits were identified through reinforcement principles analysis.
  • No gross anatomical changes or cell loss were observed at this age.

Conclusions:

  • Early cognitive dysfunction occurs in tgHD rats before the onset of motor deficits, anatomical changes, or cell loss.
  • The SORT paradigm is a sensitive tool for screening preclinical cognitive deficits in HD models.
  • This finding supports the SORT as a valuable preclinical screen for therapeutic interventions in Huntington's disease.

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