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Eric A. Horne, Jonathan Coy, Katie Swinney, Susan Fung, Allison E. T. Cherry, William R. Marrs, Alipi V. Naydenov, Yi Hsing Lin, Xiaocui Sun, C. Dirk Keene, Eric Grouzmann, Paul Muchowski, Gillian P. Bates, Ken Mackie and Nephi Stella Downregulation of cannabinoid receptor 1 from neuropeptide Y interneurons in the basal ganglia of patients with Huntington's disease and mouse models European Journal of Neuroscience 37

Article first published online: 21 NOV 2012 | DOI: 10.1111/ejn.12045

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Cannabinoid Receptor 1 (CB1 receptor) regulates several neuronal functions, including neurotransmitter release and neuronal viability, and is one of the earliest down-regulated proteins in Huntington's disease (HD). We show here that of CB1 receptor expression is down-regulated in both indirect pathway medium spiny neurons and NPY/nNOS+ interneurons in the striatum of HD mouse models and patients. CB1 receptor down-regulation in NPY/nNOS+ interneurons correlates with the presence of micro-aggregates of mutant huntingtin protein, and prevents cannabinoid mediated CREB phosphorylation in NPY/nNOS+ interneurons. CB1 receptor loss at NPY/nNOS+ interneurons could contribute to the altered GABAergic signaling present in the striatum of HD patients and ultimately to the pathogenesis of HD.

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