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Metabolic and type 1 cannabinoid receptor imaging of a transgenic rat model in the early phase of Huntington disease.
Exp Neurol 2011; 229(2):440-9EN

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 11 months. 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 10 months, 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 5 months vs. -10.9%, p<1.5×10(-5) at 10 months). 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 11 months 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.

Authors+Show Affiliations

Division of Nuclear Medicine, KU Leuven and University Hospital Leuven, Belgium. cindy.casteels@med.kuleuven.beNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21459091

Citation

Casteels, C, et al. "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, 2011, pp. 440-9.
Casteels C, Vandeputte C, Rangarajan JR, et al. Metabolic and type 1 cannabinoid receptor imaging of a transgenic rat model in the early phase of Huntington disease. Exp Neurol. 2011;229(2):440-9.
Casteels, C., Vandeputte, C., Rangarajan, J. R., Dresselaers, T., Riess, O., Bormans, G., ... Van Laere, K. (2011). Metabolic and type 1 cannabinoid receptor imaging of a transgenic rat model in the early phase of Huntington disease. Experimental Neurology, 229(2), pp. 440-9. doi:10.1016/j.expneurol.2011.03.014.
Casteels C, et al. Metabolic and Type 1 Cannabinoid Receptor Imaging of a Transgenic Rat Model in the Early Phase of Huntington Disease. Exp Neurol. 2011;229(2):440-9. PubMed PMID: 21459091.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metabolic and type 1 cannabinoid receptor imaging of a transgenic rat model in the early phase of Huntington disease. AU - Casteels,C, AU - Vandeputte,C, AU - Rangarajan,J R, AU - Dresselaers,T, AU - Riess,O, AU - Bormans,G, AU - Maes,F, AU - Himmelreich,U, AU - Nguyen,H, AU - Van Laere,K, Y1 - 2011/03/31/ PY - 2011/01/17/received PY - 2011/03/11/revised PY - 2011/03/21/accepted PY - 2011/4/5/entrez PY - 2011/4/5/pubmed PY - 2011/8/6/medline SP - 440 EP - 9 JF - Experimental neurology JO - Exp. Neurol. VL - 229 IS - 2 N2 - 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 11 months. 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 10 months, 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 5 months vs. -10.9%, p<1.5×10(-5) at 10 months). 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 11 months 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. SN - 1090-2430 UR - https://www.unboundmedicine.com/medline/citation/21459091/abstract/Metabolic_and_Type_1_cannabinoid_receptor_imaging_of_a_transgenic_rat_model_in_the_early_phase_of_Huntington_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(11)00098-7 DB - PRIME DP - Unbound Medicine ER -