Title: Widespread Decrease of Type 1 Cannabinoid Receptor Availability in Huntington Disease In Vivo
Authors: Van Laere, Koen ×
Casteels, Cindy
Dhollander, Isabel
Goffin, Karolien
Bormans, Guy
Grachev, Igor
Vandenberghe, Wim #
Issue Date: Sep-2010
Publisher: Society of Nuclear Medicine
Series Title: Journal of Nuclear Medicine vol:51 issue:9 pages:1413-1417
Article number: 10.2967/jnumed.110.077156
Abstract: The type 1 cannabinoid receptor (CB1) is a crucial modulator of synaptic transmission in the brain. Animal and postmortem human data suggest that mutant huntingtin represses CB1 transcription. Our aim was to measure CB1 levels in the brains of Huntington disease (HD) patients in vivo. Methods: Twenty symptomatic HD patients and 14 healthy controls underwent PET with the novel CB1 ligand N-[2-(3-cyano-phenyl)-3-(4-(2-F-18-fluorethoxy)phenyl)-1-methylpropyl]-2-(5-methyl-2-pyridyloxy)-2-methylproponamide. Results: We observed a profound decrease of CB1 availability throughout the gray matter of the cerebrum, cerebellum, and brain stem in HD patients, even in early disease stages. Disease burden ([number of CAG repeats in the HTT gene -35.5] x age) was inversely correlated with CB1 availability in the prefrontal and premotor cortex. Conclusion: The profound early and widespread reduction of CB1 availability in vivo is consistent with the hypothesis that mutant huntingtin represses CB1 transcription. This is the first, to our knowledge, in vivo demonstration of disturbance of the endocannabinoid system in a human neurologic disease.
ISSN: 0161-5505
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Nuclear Medicine & Molecular Imaging
Laboratory for Parkinson Research
Research Group Experimental Neurology
× corresponding author
# (joint) last author

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