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Project

Preclinical imaging of the brain cannabinoid receptors in Huntington's disease.

Huntingtons disease (HD) is a progressive neurodegenerative disorder, without effective therapy. The endocannabinoid system (ECS) is dysregulated in HD. Ex vivo studies point towards a role of the type-1 cannabinoid receptor (CB1-R) in the pathogenesis, especially on the motor, cognitive and behavioral domains. The type-2 cannabinoid receptor (CB2-R), a marker of neuroinflammation, is part of an endogenous mechanism of defense. We recently investigated brain CB1-R availability in vivo using PET. We found in HD patients that substantial cortical and subcortical decreases in CB1-R are present, related to disease burden in prefrontal areas. These findings are compatible with a disturbance of CB1-R expression by mutant-huntingtin, and may thus be present before disease onset. We also reported this in presymptomatic transgenic HD rats. In vivo studies on the CB2-R have not yet been performed. We wish to study the relative contributions of the CB1-R and CB2-R as key effectors of the ECS in the pathophysiology of experimental HD. Also, translational comparison with ongoing human HD studies will be made to investigate a proof-of-mechanism of possible ECS-based therapies. These will be applied on experimental models. Methodologically, MRI-based correction for the partial-volume-effect, and non-invasive kinetic modeling approaches will be optimized for these microPET measurements.
Date:1 Oct 2010 →  7 Nov 2016
Keywords:Type-2 cannabinoid receptor, Type-1 cannabinoid receptor, Huntington's disease, Small-animal PET
Disciplines:Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing, Medical imaging and therapy