Metabolic–dopaminergic mapping of the 6-hydroxydopamine rat model for Parkinson’s disease

  • Cindy Casteels
  • Erwin Lauwers
  • Guy Bormans
  • Veerle Baekelandt
  • Koen Van Laere
Original Article

DOI: 10.1007/s00259-007-0558-3

Cite this article as:
Casteels, C., Lauwers, E., Bormans, G. et al. Eur J Nucl Med Mol Imaging (2008) 35: 124. doi:10.1007/s00259-007-0558-3

Abstract

Purpose

The unilateral 6-hydroxydopamine (6-OHDA) lesion rat model is a well-known acute model for Parkinson’s disease (PD). Its validity has been supported by invasive histology, behavioral studies and electrophysiology. Here, we have characterized this model in vivo by multitracer imaging [glucose metabolism and dopamine transporter (DAT)] in relation to behavioral and histological parameters.

Methods

Eighteen female adult Wistar rats (eight 6-OHDA-lesioned, ten controls) were investigated using multitracer [18F]-fluoro-2-deoxy-D-glucose (FDG) and [18F]-FECT {2′-[18F]-fluoroethyl-(1R-2-exo-3-exe)-8-methyl-3-(4-chlorophenyl)-8-azabicyclo(3.2.1)-octane-2-carboxylate} small animal positron emission tomography (PET). Relative glucose metabolism and parametric DAT binding images were anatomically standardized to Paxinos space and analyzed on a voxel-basis using SPM2, supplemented by a template-based predefined volumes-of-interest approach. Behavior was characterized by the limb-use asymmetry test; dopaminergic innervation was validated by in vitro tyrosine hydroxylase staining.

Results

In the 6-OHDA model, significant glucose hypometabolism is present in the ipsilateral sensory-motor cortex (−6.3%; p = 4 × 10−6). DAT binding was severely decreased in the ipsilateral caudate-putamen, nucleus accumbens and substantia nigra (all p < 5 × 10−9), as confirmed by the behavioral and histological outcomes. Correlation analysis revealed a positive relationship between the degree of DAT impairment and the change in glucose metabolism in the ipsilateral hippocampus (p = 3 × 10−5), while cerebellar glucose metabolism was inversely correlated to the level of DAT impairment (p < 3 × 10−4).

Conclusions

In vivo cerebral mapping of 6-OHDA-lesioned rats using [18F]-FDG and [18F]-FECT small animal PET shows molecular–functional correspondence to the cortico-subcortical network impairments observed in PD patients. This provides a further molecular validation supporting the validity of the 6-OHDA lesion model to mimic multiple aspects of human PD.

Keywords

Dopamine transporter[18F]-Fluoro-2-deoxy-D-glucose6-HydroxydopamineParkinson’s diseaseSmall-animal positron emission tomography

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Cindy Casteels
    • 1
    • 2
    • 5
  • Erwin Lauwers
    • 3
  • Guy Bormans
    • 2
    • 4
  • Veerle Baekelandt
    • 3
  • Koen Van Laere
    • 1
    • 2
  1. 1.Division of Nuclear MedicineKU Leuven and University Hospital LeuvenLeuvenBelgium
  2. 2.Molecular Small Animal Imaging Center (MOSAIC)KU LeuvenLeuvenBelgium
  3. 3.Laboratory for Neurobiology and Gene TherapyKU LeuvenLeuvenBelgium
  4. 4.Laboratory for RadiopharmacyKU LeuvenLeuvenBelgium
  5. 5.Division of Nuclear MedicineKU Leuven and University Hospital GasthuisbergLeuvenBelgium