Title: Metabolic-dopaminergic mapping of the 6-hydroxydopamine rat model for Parkinson's disease
Authors: Casteels, Cindy ×
Lauwers, Erwin
Bormans, Guy
Baekelandt, Veerle
Van Laere, Koen #
Issue Date: Jan-2008
Series Title: European Journal of Nuclear Medicine and Molecular Imaging vol:35 issue:1 pages:124-134
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 [(18)F]-fluoro-2-deoxy-D: -glucose (FDG) and [(18)F]-FECT {2'-[(18)F]-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 x 10(-6)). DAT binding was severely decreased in the ipsilateral caudate-putamen, nucleus accumbens and substantia nigra (all p < 5 x 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 x 10(-5)), while cerebellar glucose metabolism was inversely correlated to the level of DAT impairment (p < 3 x 10(-4)). CONCLUSIONS: In vivo cerebral mapping of 6-OHDA-lesioned rats using [(18)F]-FDG and [(18)F]-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.
ISSN: 1619-7070
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Animal Physiology and Neurobiology Section - miscellaneous
Nuclear Medicine & Molecular Imaging
Research Group for Neurobiology and Gene Therapy
× corresponding author
# (joint) last author

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