QTL for nicotine sensitivity on Chr7 at D7Mit66 (116.91 Mbp , Build 37)
Description:
nicotine sensitivity spans 91.91 - 141.91 Mbp (NCBI Build 37) on Chr7. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for alcohol preference locus on Chr7 at D7Mit105 (126.73 Mbp , Build 37)
Description:
alcohol preference locus spans 101.73 - 151.73 Mbp (NCBI Build 37) on Chr7. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
alcohol preference locus 14, female specific at D7Mit105 with a LOD score of 1.84 (p < 0.004) spans and preference correlation of 0.591 101.73 - 151.73 Mbp (NCBI Build 37) on Chr7. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for METH responses for home cage activity on Chr7 at D7Mit12 (129.57 Mbp , Build 37)
Description:
METH responses for home cage activity spans 104.57 - 154.57 Mbp (NCBI Build 37) on Chr7. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for METH responses for body temperature on Chr7 at Xmv76 (137.02 Mbp , Build 37)
Description:
METH responses for body temperature spans 112.02 - 162.02 Mbp (NCBI Build 37) on Chr7. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Genes that are differentially expressed in response to over expressing MECP2 (causes anxiety phenotype) in the amygdala. Statistics reported as fold change.
Authors:
Samaco RC, Mandel-Brehm C, McGraw CM, Shaw CA, McGill BE, Zoghbi HY
Genes with particular expression in the Postsubiculum, layer 1. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Inferior colliculus, central nucleus. Data represent fold expression difference in structure versus grey matter average expression.
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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