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http://purl.uniprot.org/citations/25018107http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25018107http://www.w3.org/2000/01/rdf-schema#comment"Several lines of evidence imply early alterations in endocannabinoid and phosphodiesterase 10A (PDE10A) signaling in Huntington disease (HD). Using [(18)F]MK-9470 and [(18)F]JNJ42259152 small-animal positron emission tomography (PET), we investigated for the first time cerebral changes in type 1 cannabinoid (CB1) receptor binding and PDE10A levels in vivo in presymptomatic, early symptomatic, and late symptomatic HD (R6/2) mice, in relation to glucose metabolism ([(18)F]FDG PET), brain morphology (magnetic resonance imaging) and motor function. Ten R6/2 and 16 wild-type (WT) mice were investigated at 3 different time points between the age of 4 and 13 weeks. Parametric CB1 receptor and PDE10A images were anatomically standardized to Paxinos space and analyzed voxelwise. Volumetric microMRI imaging was performed to assess HD pathology. In R6/2 mice, CB1 receptor binding was decreased in comparison with WT in a cluster comprising the bilateral caudate-putamen, globus pallidus, and thalamic nucleus at week 5 (-8.1% ± 2.6%, p = 1.7 × 10(-5)). Longitudinal follow-up showed further progressive decline compared with controls in a cluster comprising the bilateral hippocampus, caudate-putamen, globus pallidus, superior colliculus, thalamic nucleus, and cerebellum (late vs. presymptomatic age: -13.7% ± 3.1% for R6/2 and +1.5% ± 4.0% for WT, p = 1.9 × 10(-5)). In R6/2 mice, PDE10A binding potential also decreased over time to reach significance at early and late symptomatic HD (late vs. presymptomatic age: -79.1% ± 1.9% for R6/2 and +2.1% ± 2.7% for WT, p = 1.5 × 10(-4)). The observed changes in CB1 receptor and PDE10A binding were correlated to anomalies exhibited by R6/2 animals in motor function, whereas no correlation was found with magnetic resonance imaging-based striatal volume. Our findings point to early regional dysfunctions in endocannabinoid and PDE10A signaling, involving the caudate-putamen and lateral globus pallidus, which may play a role in the progression of the disease in R6/2 animals. PET quantification of in vivo CB1 and/or PDE10A binding may thus be useful early biomarkers for HD. Our results also provide evidence of subtle motor deficits at earlier stages than previously described."xsd:string
http://purl.uniprot.org/citations/25018107http://purl.org/dc/terms/identifier"doi:10.1016/j.neurobiolaging.2014.06.010"xsd:string
http://purl.uniprot.org/citations/25018107http://purl.uniprot.org/core/author"Ooms M."xsd:string
http://purl.uniprot.org/citations/25018107http://purl.uniprot.org/core/author"Himmelreich U."xsd:string
http://purl.uniprot.org/citations/25018107http://purl.uniprot.org/core/author"Bormans G."xsd:string
http://purl.uniprot.org/citations/25018107http://purl.uniprot.org/core/author"Casteels C."xsd:string
http://purl.uniprot.org/citations/25018107http://purl.uniprot.org/core/author"Van Laere K."xsd:string
http://purl.uniprot.org/citations/25018107http://purl.uniprot.org/core/author"Maes F."xsd:string
http://purl.uniprot.org/citations/25018107http://purl.uniprot.org/core/author"Fernandez-Ruiz J."xsd:string
http://purl.uniprot.org/citations/25018107http://purl.uniprot.org/core/author"Valdeolivas S."xsd:string
http://purl.uniprot.org/citations/25018107http://purl.uniprot.org/core/author"Rangarajan J.R."xsd:string
http://purl.uniprot.org/citations/25018107http://purl.uniprot.org/core/author"Rietjens R."xsd:string
http://purl.uniprot.org/citations/25018107http://purl.uniprot.org/core/author"Vunckx K."xsd:string
http://purl.uniprot.org/citations/25018107http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/25018107http://purl.uniprot.org/core/name"Neurobiol Aging"xsd:string
http://purl.uniprot.org/citations/25018107http://purl.uniprot.org/core/pages"2858-2869"xsd:string
http://purl.uniprot.org/citations/25018107http://purl.uniprot.org/core/title"Early decrease of type 1 cannabinoid receptor binding and phosphodiesterase 10A activity in vivo in R6/2 Huntington mice."xsd:string
http://purl.uniprot.org/citations/25018107http://purl.uniprot.org/core/volume"35"xsd:string
http://purl.uniprot.org/citations/25018107http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25018107
http://purl.uniprot.org/citations/25018107http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/25018107
http://purl.uniprot.org/uniprot/#_A0A385KNU8-mappedCitation-25018107http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25018107
http://purl.uniprot.org/uniprot/#_A0A3B2W3N3-mappedCitation-25018107http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25018107
http://purl.uniprot.org/uniprot/#_A0A3B2WCR8-mappedCitation-25018107http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25018107
http://purl.uniprot.org/uniprot/#_A0A384DV92-mappedCitation-25018107http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25018107
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