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

被引:38
作者
Casteels, Cindy
Lauwers, Erwin
Bormans, Guy
Baekelandt, Veerle
Van Laere, Koen
机构
[1] Katholieke Univ Leuven, Div Nucl Med, B-3000 Louvain, Belgium
[2] Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium
[3] Univ Hosp Leuven, Louvain, Belgium
[4] Katholieke Univ Leuven, MOSAIC, Louvain, Belgium
[5] Katholieke Univ Leuven, Lab Neurobiol & Gene Therapy, Louvain, Belgium
[6] Katholieke Univ Leuven, Lab Radiopharm, Louvain, Belgium
关键词
dopamine transporter; F-18]-fluoro-2-deoxy-D-glucose; 6-hydroxydopamine; Parkinson's disease; small-animal positron emission tomography;
D O I
10.1007/s00259-007-0558-3
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
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 [F-18]-fluoro-2-deoxy-D-glucose (FDG) and [F-18]-FECT {2'-[F-18]-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)). Coclusions In vivo cerebral mapping of 6-OHDA-lesioned rats using [F-18]-FDG and [F-18]-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.
引用
收藏
页码:124 / 134
页数:11
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