Title: Metabolic and Type 1 cannabinoid receptor imaging of a transgenic rat model in the early phase of Huntington disease
Authors: Casteels, Cindy ×
Vandeputte, Caroline
Rangarajan, Janaki Raman
Dresselaers, Tom
Riess, O
Bormans, Guy
Maes, Frederik
Himmelreich, Uwe
Nguyen, H
Van Laere, Koen #
Issue Date: Jun-2011
Publisher: Academic Press
Series Title: Experimental Neurology vol:229 issue:2 pages:440-449
Abstract: Several lines of evidence imply early alterations in metabolic and endocannabinoid neurotransmission in Huntington disease (HD). Using [(18)F]MK-9470 and small animal PET, we investigated for the first time cerebral changes in type 1 cannabinoid (CB1) receptor binding in vivo in pre-symptomatic and early symptomatic rats of HD (tgHD), in relation to glucose metabolism, morphology and behavioral testing for motor and cognitive function. Twenty-three Sprague-Dawley rats (14 tgHD and 9 wild-types) were investigated between the age of 2 and 11months. Relative glucose metabolism and parametric CB1 receptor images were anatomically standardized to Paxinos space and analyzed voxel-wise. Volumetric microMRI imaging was performed to assess HD neuropathology. Within the first 10months, bilateral volumes of caudate-putamen and lateral ventricles did not significantly differ between genotypes. Longitudinal- and genotype evolution showed that relative [(18)F]MK-9470 binding progressively decreased in the caudate-putamen and lateral globus pallidus of tgHD rats (-8.3%, p≤1.1×10(-5) at 5months vs. -10.9%, p<1.5×10(-5) at 10months). In addition, relative glucose metabolism increased in the bilateral sensorimotor cortex of 2-month-old tgHD rats (+8.1%, p≤1.5×10(-5)), where it was positively correlated to motor function at that time point. TgHD rats developed cognitive deficits at 6 and 11months of age. Our findings point to early regional dysfunctions in endocannabinoid signalling, involving the lateral globus pallidus and caudate-putamen. In vivo CB1 receptor measurements using [(18)F]MK-9470 may thus be a useful early biomarker for HD. Our results also provide evidence of subtle motor and cognitive deficits at earlier stages than previously described.
Description: Casteels C., Vandeputte C., Rangarajan J.R., Dresselaers T., Riess O., Bormans G., Maes F., Himmelreich U., Nguyen H., Van Laere K., ''Metabolic and type 1 cannabinoid receptor imaging of a transgenic rat model in the early phase of Huntington disease'', Experimental neurology, vol. 229, no. 2, pp. 440-449, June 2011.
ISSN: 0014-4886
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Nuclear Medicine & Molecular Imaging
Biomedical MRI
Radiopharmaceutical Research
ESAT - PSI, Processing Speech and Images
× corresponding author
# (joint) last author

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