Abstract
Transcriptional dysregulation is a major pathological feature of Huntington's disease (HD). The goal of this study was to understand how p65/RelA co-regulated genes, specifically those of the cytokine and endocannabinoid systems, were affected in HD. p65/RelA levels were lower in human HD tissue and R6/2 HD mice, as were the levels of the type 1 cannabinoid receptor (CB1), IL-1β, IL-8, CCL5, GM-CSF, MIP-1β, and TNFα, all of which may be regulated by p65/RelA. Activation of p65/RelA restored CB1 and CCL5 expression in STHdh cell models of HD. Therefore, p65/RelA activation may normalize the expression of some genes in HD.
Keywords:
Cannabinoid; Cytokine; Huntington's disease; NF-κB p65/RelA; Neuroinflammation.
Copyright © 2013 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Age Factors
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Aged
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Amidohydrolases / genetics
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Amidohydrolases / metabolism
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Animals
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Arachidonic Acids / pharmacology
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Cannabinoids / pharmacology
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Cells, Cultured
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Corpus Striatum / cytology
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Corpus Striatum / metabolism*
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Cytokines / genetics
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Cytokines / metabolism*
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Disease Models, Animal
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Endocannabinoids / agonists
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Endocannabinoids / antagonists & inhibitors
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Endocannabinoids / metabolism*
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Enzyme Inhibitors / pharmacology
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Female
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology
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Humans
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Huntingtin Protein
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Huntington Disease / pathology*
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Indoles / pharmacology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Middle Aged
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NF-kappa B / genetics
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NF-kappa B / metabolism*
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Nerve Tissue Proteins / genetics
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Neurons / drug effects
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Neurons / metabolism
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Nuclear Proteins / genetics
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Receptor, Cannabinoid, CB1 / genetics
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Receptor, Cannabinoid, CB1 / metabolism
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Transcription Factor RelA / genetics
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Transcription Factor RelA / metabolism*
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Trinucleotide Repeats / genetics
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Young Adult
Substances
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Arachidonic Acids
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Cannabinoids
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Cytokines
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Endocannabinoids
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Enzyme Inhibitors
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Htt protein, mouse
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Huntingtin Protein
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Indoles
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NF-kappa B
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Nerve Tissue Proteins
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Nuclear Proteins
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Receptor, Cannabinoid, CB1
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Transcription Factor RelA
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arachidonyl-2-chloroethylamide
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HU 308
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Amidohydrolases
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fatty-acid amide hydrolase
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iodopravadoline