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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  <identifier identifierType="URL">https://zenodo.org/record/16298</identifier>
  <creators>
    <creator>
      <creatorName>Ooms, Maarten</creatorName>
      <givenName>Maarten</givenName>
      <familyName>Ooms</familyName>
      <affiliation>Laboratory for Radiopharmacy, KU Leuven, Belgium and MoSAIC, Molecular Small Animal Imaging Centre, KU Leuven, Belgium</affiliation>
    </creator>
    <creator>
      <creatorName>Rietjens, Roma</creatorName>
      <givenName>Roma</givenName>
      <familyName>Rietjens</familyName>
      <affiliation>MoSAIC, Molecular Small Animal Imaging Centre, KU Leuven, Belgium and Division of Nuclear Medicine, KU Leuven and University Hospital Leuven, Belgium</affiliation>
    </creator>
    <creator>
      <creatorName>Rangarajan, Janaki Raman</creatorName>
      <givenName>Janaki Raman</givenName>
      <familyName>Rangarajan</familyName>
      <affiliation>KU Leuven Medical Image Computing (ESAT/PSI), Department of Electrical Engineering &amp; Medical Imaging Research Center, University Hospital Leuven, Belgium</affiliation>
    </creator>
    <creator>
      <creatorName>Vunckx, Kathleen</creatorName>
      <givenName>Kathleen</givenName>
      <familyName>Vunckx</familyName>
      <affiliation>Division of Nuclear Medicine, KU Leuven and University Hospital Leuven, Belgium</affiliation>
    </creator>
    <creator>
      <creatorName>Valdeolivas, Sara</creatorName>
      <givenName>Sara</givenName>
      <familyName>Valdeolivas</familyName>
      <affiliation>Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Maes, Frederik</creatorName>
      <givenName>Frederik</givenName>
      <familyName>Maes</familyName>
      <affiliation>KU Leuven Medical Image Computing (ESAT/PSI), Department of Electrical Engineering &amp; Medical Imaging Research Center, University Hospital Leuven, Belgium</affiliation>
    </creator>
    <creator>
      <creatorName>Himmelreich, Uwe</creatorName>
      <givenName>Uwe</givenName>
      <familyName>Himmelreich</familyName>
      <affiliation>Biomedical NMR Unit, KU Leuven, Belgium</affiliation>
    </creator>
    <creator>
      <creatorName>Fernandez-Ruiz, Javier</creatorName>
      <givenName>Javier</givenName>
      <familyName>Fernandez-Ruiz</familyName>
      <affiliation>Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Bormans, Guy</creatorName>
      <givenName>Guy</givenName>
      <familyName>Bormans</familyName>
      <affiliation>Laboratory for Radiopharmacy, KU Leuven, Belgium and MoSAIC, Molecular Small Animal Imaging Centre, KU Leuven, Belgium</affiliation>
    </creator>
    <creator>
      <creatorName>Van Laere, Koen</creatorName>
      <givenName>Koen</givenName>
      <familyName>Van Laere</familyName>
      <affiliation>MoSAIC, Molecular Small Animal Imaging Centre, KU Leuven, Belgium and Division of Nuclear Medicine, KU Leuven and University Hospital Leuven, Belgium</affiliation>
    </creator>
    <creator>
      <creatorName>Casteels, Cindy</creatorName>
      <givenName>Cindy</givenName>
      <familyName>Casteels</familyName>
      <affiliation>MoSAIC, Molecular Small Animal Imaging Centre, KU Leuven, Belgium and Division of Nuclear Medicine, KU Leuven and University Hospital Leuven, Belgium</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Early decrease of type 1 cannabinoid receptor binding and phosphodiesterase 10A activity in vivo in R6/2 Huntington mice.</title>
  </titles>
  <publisher>Zenodo</publisher>
  <publicationYear>2014</publicationYear>
  <subjects>
    <subject>Type 1 cannabinoid receptor, ,, , </subject>
    <subject>phosphodiesterase 10A</subject>
    <subject> Huntington disease</subject>
    <subject>small-animal PET</subject>
    <subject>R6/2 mice</subject>
  </subjects>
  <dates>
    <date dateType="Issued">2014-06-16</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://zenodo.org/record/16298</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1016/j.neurobiolaging.2014.06.010</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/inmind</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/ecfunded</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="https://creativecommons.org/publicdomain/zero/1.0/legalcode">Creative Commons Zero v1.0 Universal</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">&lt;p&gt;Purpose: Several lines of evidence imply early alterations in endocannabinoid and phosphodiesterase&amp;nbsp;10A (PDE10A) signaling in Huntington disease (HD). Using [18F]MK-9470 and [18F]JNJ42259152&amp;nbsp;small-animal PET, we investigated for the first time cerebral changes in type 1 cannabinoid (CB1)&amp;nbsp;receptor binding and PDE10A levels in vivo in pre-, early- and late symptomatic HD (R6/2) mice, in&amp;nbsp;relation to glucose metabolism ([18F]FDG PET), brain morphology (MRI) and motor function.&amp;nbsp;&lt;/p&gt;

&lt;p&gt;Methods:&amp;nbsp;Ten R6/2 and 16 wild-type (WT) mice were investigated at 3 different time points between the age of 4&amp;nbsp;and 13 weeks. Parametric CB1 receptor and PDE10A images were anatomically standardized to&amp;nbsp;Paxinos space and analyzed voxel-wise. Volumetric microMRI imaging was performed to assess HD&amp;nbsp;pathology.&amp;nbsp;&lt;/p&gt;

&lt;p&gt;Results: In R6/2 mice, CB1 receptor binding was decreased in comparison to WT in a&amp;nbsp;cluster comprising the bilateral caudate-putamen, globus pallidus and thalamic nucleus at week 5 (-8.1&amp;plusmn;2.6%; p=1.7.10-5). Longitudinal follow-up showed further progressive decline compared to controls&amp;nbsp;in a cluster comprising the bilateral hippocampus, caudate-putamen, globus pallidus, superior&amp;nbsp;colliculus, thalamic nucleus and cerebellum (late vs. presymptomatic age: -13.7&amp;plusmn;3.1% for R6/2 and&amp;nbsp;+1.5&amp;plusmn;4.0% for WT; p=1.9.10-5). In R6/2 mice, PDE10A binding potential also decreased over time, to&amp;nbsp;reach significance at early and late symptomatic HD (late vs. presymptomatic age: -79.1&amp;plusmn;1.9% for&amp;nbsp;R6/2 and +2.1&amp;plusmn;2.7% for WT; p=1.5.10-4). The observed changes in CB1 receptor and PDE10A binding&amp;nbsp;were correlated to anomalies exhibited by R6/2 animals in motor function, while no correlation was&amp;nbsp;found with MRI-based striatal volume.&amp;nbsp;&lt;/p&gt;

&lt;p&gt;Conclusion: Our findings point to early regional dysfunctions in&amp;nbsp;endocannabinoid and PDE10A signaling, involving the caudate-putamen and lateral globus pallidus,&amp;nbsp;that may play a role in the progression of the disease in R6/2 animals. PET quantification of in vivo&amp;nbsp;CB1 and/or PDE10A binding may thus be useful early biomarkers for HD. Our results also provide&amp;nbsp;evidence of subtle motor deficits at earlier stages than previously described.&lt;/p&gt;</description>
  </descriptions>
  <fundingReferences>
    <fundingReference>
      <funderName>European Commission</funderName>
      <funderIdentifier funderIdentifierType="Crossref Funder ID">10.13039/501100000780</funderIdentifier>
      <awardNumber awardURI="info:eu-repo/grantAgreement/EC/FP7/278850/">278850</awardNumber>
      <awardTitle>Imaging of Neuroinflammation in Neurodegenerative Diseases</awardTitle>
    </fundingReference>
  </fundingReferences>
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