Renthal W, Kumar A, Xiao G, Wilkinson M, Covington HE 3rd, Maze I, Sikder D, Robison AJ, LaPlant Q, Dietz DM, Russo SJ, Vialou V, Chakravarty S, Kodadek TJ, Stack A, Kabbaj M, Nestler EJ
Genes with particular expression in the Nucleus of the lateral lemniscus, dorsal part. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Nucleus of the lateral lemniscus, horizontal part. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Interposed nucleus. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Superior olivary complex, medial part. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Koelliker-Fuse subnucleus. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Infralimbic area, layer 1. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Anterior olfactory nucleus, dorsal part. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Accessory olfactory bulb, glomerular layer. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Orbital area, lateral part, layer 1. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Orbital area, medial part, layer 1. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Cochlear nucleus, subpedunclular granular region. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Motor nucleus of trigeminal. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Parabigeminal nucleus. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the External cuneate nucleus. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Nodulus (X), molecular layer. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Nodulus (X), granular layer. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Fasciola cinerea. Data represent fold expression difference in structure versus grey matter average expression.
Used chromatin immunoprecipitation coupled with promoter microarray analysis to characterize genome-wide H3K9/K27 dimethyl changes in the mouse nucleus accumbens after repeated cocaine administration.
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. Although prescribed for dyslipidemia and type-II diabetes, PPAR agonists also possess anti-addictive characteristics. PPAR agonists decrease ethanol consumption and reduce withdrawal severity and susceptibility to stress-induced relapse in rodents. However, the cellular and molecular mechanisms facilitating these properties have yet to be investigated. We tested three PPAR agonists in a continuous access two-bottle choice (2BC) drinking paradigm and found that tesaglitazar (PPARα/γ; 1.5 mg/kg) and fenofibrate (PPARα; 150 mg/kg) decreased ethanol consumption in male C57BL/6J mice while bezafibrate (PPARα/γ/β; 75 mg/kg) did not. We hypothesized that changes in brain gene expression following fenofibrate and tesaglitazar treatment lead to reduced ethanol drinking. We studied unbiased genomic profiles in areas of the brain known to be important for ethanol dependence, the prefrontal cortex (PFC) and amygdala, and also profiled gene expression in liver. Genomic profiles from the non-effective bezafibrate treatment were used to filter out genes not associated with ethanol consumption. Because PPAR agonists are anti-inflammatory, they would be expected to target microglia and astrocytes. Surprisingly, PPAR agonists produced a strong neuronal signature in mouse brain, and fenofibrate and tesaglitazar (but not bezafibrate) targeted a subset of GABAergic interneurons in the amygdala. Weighted gene co-expression network analysis (WGCNA) revealed co-expression of treatment-significant genes. Functional annotation of these gene networks suggested that PPAR agonists might act via neuropeptide and dopaminergic signaling pathways in the amygdala. Our results reveal gene targets through which PPAR agonists can affect alcohol consumption behavior.
Authors:
Laura B Ferguson, Dana Most, Yuri A Blednov, R Adron Harris
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. Although prescribed for dyslipidemia and type-II diabetes, PPAR agonists also possess anti-addictive characteristics. PPAR agonists decrease ethanol consumption and reduce withdrawal severity and susceptibility to stress-induced relapse in rodents. However, the cellular and molecular mechanisms facilitating these properties have yet to be investigated. We tested three PPAR agonists in a continuous access two-bottle choice (2BC) drinking paradigm and found that tesaglitazar (PPARα/γ; 1.5 mg/kg) and fenofibrate (PPARα; 150 mg/kg) decreased ethanol consumption in male C57BL/6J mice while bezafibrate (PPARα/γ/β; 75 mg/kg) did not. We hypothesized that changes in brain gene expression following fenofibrate and tesaglitazar treatment lead to reduced ethanol drinking. We studied unbiased genomic profiles in areas of the brain known to be important for ethanol dependence, the prefrontal cortex (PFC) and amygdala, and also profiled gene expression in liver. Genomic profiles from the non-effective bezafibrate treatment were used to filter out genes not associated with ethanol consumption. Because PPAR agonists are anti-inflammatory, they would be expected to target microglia and astrocytes. Surprisingly, PPAR agonists produced a strong neuronal signature in mouse brain, and fenofibrate and tesaglitazar (but not bezafibrate) targeted a subset of GABAergic interneurons in the amygdala. Weighted gene co-expression network analysis (WGCNA) revealed co-expression of treatment-significant genes. Functional annotation of these gene networks suggested that PPAR agonists might act via neuropeptide and dopaminergic signaling pathways in the amygdala. Our results reveal gene targets through which PPAR agonists can affect alcohol consumption behavior.
Authors:
Laura B Ferguson, Dana Most, Yuri A Blednov, R Adron Harris
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