Genotype specific age related changes in a transgenic rat model of Huntington's disease

Neuroimage. 2011 Oct 15;58(4):1006-16. doi: 10.1016/j.neuroimage.2011.07.007. Epub 2011 Jul 13.

Abstract

We aimed to characterize the transgenic Huntington rat model with in vivo imaging and identify sensitive and reliable biomarkers associated with early and progressive disease status. In order to do so, we performed a multimodality (DTI and PET) longitudinal imaging study, during which the same TgHD and wildtype (Wt) rats were repetitively scanned. Surprisingly, the relative ventricle volume was smaller but increased faster in TgHD compared to Wt animals. DTI (mean, axial, radial diffusivity) revealed subtle genotype-specific aging effects in the striatum and its surrounding white matter, already in the presymptomatic stage. Using ¹⁸F-FDG and ¹⁸F-Fallypride PET imaging, we were not able to demonstrate genotype-specific aging effects within the striatum. The outcome of this longitudinal study was somewhat surprising as it demonstrated a significant differential aging pattern in TgHD versus Wt animals. Although it seems that the TgHD rat model does not have a sufficient expression of disease yet at the age of 12 months, further validation of this model is highly beneficial since there is still an incomplete understanding of the early disease mechanisms of Huntington's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / pathology*
  • Animals
  • Autoradiography
  • Benzamides
  • Biomarkers
  • Brain / diagnostic imaging
  • Brain / pathology
  • Cerebral Ventricles / diagnostic imaging
  • Cerebral Ventricles / pathology
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / pathology
  • Diffusion Tensor Imaging
  • Fluorodeoxyglucose F18
  • Genotype
  • Huntington Disease / diagnostic imaging
  • Huntington Disease / genetics*
  • Huntington Disease / pathology
  • Image Processing, Computer-Assisted
  • Male
  • Phenotype
  • Positron-Emission Tomography
  • Pyrrolidines
  • Radiopharmaceuticals
  • Rats
  • Rats, Transgenic

Substances

  • Benzamides
  • Biomarkers
  • N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide
  • Pyrrolidines
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18