Cerebellum Gene Expression Correlates for OF_CORNER_TIME_PCT measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The OF_CORNER_TIME_PCT measures Open Field - Total time in corners under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Cerebellum Gene Expression Correlates for OF_PERIM_LESS_CORNER measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The OF_PERIM_LESS_CORNER measures Open Field - Total time in perimeter less corner under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Cerebellum Gene Expression Correlates for COCA_TEST_DRUG measured in BXD RI Females & Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The COCA_TEST_DRUG measures Cocaine CPP- Time (s) in drug-paired compartment a under the domain Cocaine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Cerebellum Gene Expression Correlates for COCA_TEST_VEHICLE measured in BXD RI Females & Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The COCA_TEST_VEHICLE measures Cocaine CPP - Time (s) in saline paired compartment a under the domain Cocaine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Cerebellum Gene Expression Correlates for COCA_TEST_VEHICLE measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The COCA_TEST_VEHICLE measures Cocaine CPP - Time (s) in saline paired compartment a under the domain Cocaine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Cerebellum Gene Expression Correlates for COCA_TIME_PCT_CHANGE measured in BXD RI Females & Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The COCA_TIME_PCT_CHANGE measures Cocaine CPP - difference in percent test time spent relative to preconditioning under the domain Cocaine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
QTL for activity response to ethanol on Chr2 at NA (80.10 Mbp , Build 37)
Description:
activity response to ethanol spans 55.10 - 105.10 Mbp (NCBI Build 37) on Chr2. 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 ethanol response acute on Chr2 at NA (80.10 Mbp , Build 37)
Description:
ethanol response acute spans 55.10 - 105.10 Mbp (NCBI Build 37) on Chr2. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Demarest K, McCaughran J Jr, Mahjubi E, Cipp L, Hitzemann R
QTL for ethanol consumption on Chr2 at D2Mit14 (88.50 Mbp , Build 37)
Description:
ethanol consumption spans 63.50 - 113.50 Mbp (NCBI Build 37) on Chr2. 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 ethanol induced locomotor activity on Chr2 at D2Mit94 (94.37 Mbp , Build 37)
Description:
ethanol induced locomotor activity spans 69.37 - 119.37 Mbp (NCBI Build 37) on Chr2. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Hitzemann R, Cipp L, Demarest K, Mahjubi E, McCaughran J Jr
QTL for activity response to ethanol on Chr2 at NA (129.21 Mbp , Build 37)
Description:
activity response to ethanol spans 104.21 - 154.21 Mbp (NCBI Build 37) on Chr2. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
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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