Journal article Open Access

Early decrease of type 1 cannabinoid receptor binding and phosphodiesterase 10A activity in vivo in R6/2 Huntington mice.

Ooms, Maarten; Rietjens, Roma; Rangarajan, Janaki Raman; Vunckx, Kathleen; Valdeolivas, Sara; Maes, Frederik; Himmelreich, Uwe; Fernandez-Ruiz, Javier; Bormans, Guy; Van Laere, Koen; Casteels, Cindy


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    "embargo_date": "2015-06-16", 
    "doi": "10.1016/j.neurobiolaging.2014.06.010", 
    "description": "<p>Purpose: Several lines of evidence imply early alterations in endocannabinoid and phosphodiesterase&nbsp;10A (PDE10A) signaling in Huntington disease (HD). Using [18F]MK-9470 and [18F]JNJ42259152&nbsp;small-animal PET, we investigated for the first time cerebral changes in type 1 cannabinoid (CB1)&nbsp;receptor binding and PDE10A levels in vivo in pre-, early- and late symptomatic HD (R6/2) mice, in&nbsp;relation to glucose metabolism ([18F]FDG PET), brain morphology (MRI) and motor function.&nbsp;</p>\n\n<p>Methods:&nbsp;Ten R6/2 and 16 wild-type (WT) mice were investigated at 3 different time points between the age of 4&nbsp;and 13 weeks. Parametric CB1 receptor and PDE10A images were anatomically standardized to&nbsp;Paxinos space and analyzed voxel-wise. Volumetric microMRI imaging was performed to assess HD&nbsp;pathology.&nbsp;</p>\n\n<p>Results: In R6/2 mice, CB1 receptor binding was decreased in comparison to WT in a&nbsp;cluster comprising the bilateral caudate-putamen, globus pallidus and thalamic nucleus at week 5 (-8.1&plusmn;2.6%; p=1.7.10-5). Longitudinal follow-up showed further progressive decline compared to controls&nbsp;in a cluster comprising the bilateral hippocampus, caudate-putamen, globus pallidus, superior&nbsp;colliculus, thalamic nucleus and cerebellum (late vs. presymptomatic age: -13.7&plusmn;3.1% for R6/2 and&nbsp;+1.5&plusmn;4.0% for WT; p=1.9.10-5). In R6/2 mice, PDE10A binding potential also decreased over time, to&nbsp;reach significance at early and late symptomatic HD (late vs. presymptomatic age: -79.1&plusmn;1.9% for&nbsp;R6/2 and +2.1&plusmn;2.7% for WT; p=1.5.10-4). The observed changes in CB1 receptor and PDE10A binding&nbsp;were correlated to anomalies exhibited by R6/2 animals in motor function, while no correlation was&nbsp;found with MRI-based striatal volume.&nbsp;</p>\n\n<p>Conclusion: Our findings point to early regional dysfunctions in&nbsp;endocannabinoid and PDE10A signaling, involving the caudate-putamen and lateral globus pallidus,&nbsp;that may play a role in the progression of the disease in R6/2 animals. PET quantification of in vivo&nbsp;CB1 and/or PDE10A binding may thus be useful early biomarkers for HD. Our results also provide&nbsp;evidence of subtle motor deficits at earlier stages than previously described.</p>", 
    "license": {
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    "title": "Early decrease of type 1 cannabinoid receptor binding and phosphodiesterase 10A activity in vivo in R6/2 Huntington mice.", 
    "journal": {
      "volume": "35", 
      "year": "2014", 
      "issue": "12", 
      "pages": "2858-69", 
      "title": "Neurobiol Aging. "
    }, 
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        }, 
        "title": "Imaging of Neuroinflammation in Neurodegenerative Diseases", 
        "acronym": "INMIND", 
        "program": "FP7", 
        "funder": {
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          "acronyms": [], 
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    "keywords": [
      "Type 1 cannabinoid receptor, ,, , ", 
      "phosphodiesterase 10A", 
      " Huntington disease", 
      "small-animal PET", 
      "R6/2 mice"
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    "publication_date": "2014-06-16", 
    "creators": [
      {
        "affiliation": "Laboratory for Radiopharmacy, KU Leuven, Belgium and MoSAIC, Molecular Small Animal Imaging Centre, KU Leuven, Belgium", 
        "name": "Ooms, Maarten"
      }, 
      {
        "affiliation": "MoSAIC, Molecular Small Animal Imaging Centre, KU Leuven, Belgium and Division of Nuclear Medicine, KU Leuven and University Hospital Leuven, Belgium", 
        "name": "Rietjens, Roma"
      }, 
      {
        "affiliation": "KU Leuven Medical Image Computing (ESAT/PSI), Department of Electrical Engineering & Medical Imaging Research Center, University Hospital Leuven, Belgium", 
        "name": "Rangarajan, Janaki Raman"
      }, 
      {
        "affiliation": "Division of Nuclear Medicine, KU Leuven and University Hospital Leuven, Belgium", 
        "name": "Vunckx, Kathleen"
      }, 
      {
        "affiliation": "Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), Madrid, Spain", 
        "name": "Valdeolivas, Sara"
      }, 
      {
        "affiliation": "KU Leuven Medical Image Computing (ESAT/PSI), Department of Electrical Engineering & Medical Imaging Research Center, University Hospital Leuven, Belgium", 
        "name": "Maes, Frederik"
      }, 
      {
        "affiliation": "Biomedical NMR Unit, KU Leuven, Belgium", 
        "name": "Himmelreich, Uwe"
      }, 
      {
        "affiliation": "Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), Madrid, Spain", 
        "name": "Fernandez-Ruiz, Javier"
      }, 
      {
        "affiliation": "Laboratory for Radiopharmacy, KU Leuven, Belgium and MoSAIC, Molecular Small Animal Imaging Centre, KU Leuven, Belgium", 
        "name": "Bormans, Guy"
      }, 
      {
        "affiliation": "MoSAIC, Molecular Small Animal Imaging Centre, KU Leuven, Belgium and Division of Nuclear Medicine, KU Leuven and University Hospital Leuven, Belgium", 
        "name": "Van Laere, Koen"
      }, 
      {
        "affiliation": "MoSAIC, Molecular Small Animal Imaging Centre, KU Leuven, Belgium and Division of Nuclear Medicine, KU Leuven and University Hospital Leuven, Belgium", 
        "name": "Casteels, Cindy"
      }
    ], 
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