Abstract
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Objectives A dysfunctional endocannabinoid system (ECS) is implicated in early Huntington’s disease (HD). Using microPET and [18F]MK-9470 for in vivo imaging of the CB1 receptor, we investigated whether the ECS is dysfunctional in early transgenic rats of HD (tgHD), in relation to glucose metabolism ([18F]-FDG) and behavior.
Methods 24 male rats (14 tgHD, 10 wild-types (WT)) were investigated at the age of 2 and 5 months. MicroPET acquisitions were conducted on a Focus220. MicroMRI imaging was performed to assess neuronal cell death. Behavioral testing was done for motor coordination (rotarod), gait pattern (Catwalk), anxiety (elevated plus maze), and working memory (radial arm maze).
Results The first 5 months, volumes of caudate-putamen (CPu) bilaterally were not different between tgHD and WT rats. When comparing tgHD rats to WTs over time, relative [18F]MK-9470 binding decreased in the pons and cerebellum of tgHD rats (-13.1%; p=3.4x10-4). [18F]-FDG was increased in the sensorimotor cortex (+13.8%; p=4.0x10-5). Longitudinal comparison within each group showed bilaterally decreased relative [18F]MK-9470 binding in the CPu upon ageing (>5%; p<2.7x10-3). At the age of 2 months, tgHD rats showed hyperkinesia (swing speed;+27.3%; p<0.03), while working memory declined at 5 months (-328%; p=0.003).
Conclusions In vivo cerebral mapping of early symptomatic tgHD rats using [18F]MK-9470 and [18F]-FDG microPET points to potential early dysfunctions in endocannabinoid signalling, involving the pons and cerebellum, and a metabolic upregulation in the sensorimotor cortex. Our results also provide evidence of subtle motor/cognitive deficits at earlier stages than previously described.
Research Support Flemish Fund for Scientific Research (FWO/G.0548.06) and EU FP6-project DiMI (LSHB-CT-2005-512146).
- © 2009 by Society of Nuclear Medicine