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Downregulation of <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content><jats:sub>1<\/jats:sub> expression in the basal ganglia of patients with Huntington's disease (<jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>) and animal models represents one of the earliest molecular events induced by mutant huntingtin (m<jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>tt). This early disruption of neuronal <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content><jats:sub>1<\/jats:sub> signaling is thought to contribute to <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> symptoms and neurodegeneration. Here we determined whether <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content><jats:sub>1<\/jats:sub> downregulation measured in patients with <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> and mouse models was ubiquitous or restricted to specific striatal neuronal subpopulations. Using unbiased semi\u2010quantitative immunohistochemistry, we confirmed previous studies showing that <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content><jats:sub>1<\/jats:sub> expression is downregulated in medium spiny neurons of the indirect pathway, and found that <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content><jats:sub>1<\/jats:sub> is also downregulated in neuropeptide <jats:styled-content style=\"fixed-case\">Y<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">NPY<\/jats:styled-content>)\/neuronal nitric oxide synthase (n<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>)\u2010expressing interneurons while remaining unchanged in parvalbumin\u2010 and calretinin\u2010expressing interneurons. <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content><jats:sub>1<\/jats:sub> downregulation in striatal <jats:styled-content style=\"fixed-case\">NPY<\/jats:styled-content>\/n<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>\u2010expressing interneurons occurs in <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>6\/2 mice, <jats:italic>Hdh<\/jats:italic><jats:sup>Q150\/Q150<\/jats:sup> mice and the caudate nucleus of patients with <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>. In <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>6\/2 mice, <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content><jats:sub>1<\/jats:sub> downregulation in <jats:styled-content style=\"fixed-case\">NPY<\/jats:styled-content>\/n<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>\u2010expressing interneurons correlates with diffuse expression of m<jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>tt in the soma. This downregulation also occludes the ability of cannabinoid agonists to activate the pro\u2010survival signaling molecule c<jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content> response element\u2010binding protein in NPY\/n<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>\u2010expressing interneurons. Loss of <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content><jats:sub>1<\/jats:sub> signaling in <jats:styled-content style=\"fixed-case\">NPY<\/jats:styled-content>\/n<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>\u2010expressing interneurons could contribute to the impairment of basal ganglia functions linked to <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/ejn.12045","type":"journal-article","created":{"date-parts":[[2012,11,21]],"date-time":"2012-11-21T10:17:22Z","timestamp":1353493042000},"page":"429-440","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Downregulation of cannabinoid receptor 1 from neuropeptide <scp>Y<\/scp> interneurons in the basal ganglia of patients with Huntington's disease and mouse models"],"prefix":"10.1111","volume":"37","author":[{"given":"Eric A.","family":"Horne","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Washington 1959\u00a0N.E. 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