The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains.
Authors:
Samuel J Harp, Mariangela Martini, Will Rosenow, Larry D Mesner, Hugh Johnson, Charles R Farber, Emilie F Rissman
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
The GEO2R tool was used to analyze microarray data from lungs of mice either mock-infected or infected with SARS-CoV1. The Gene sets used in the analysis were from GSE59185. GEO2R was used with default parameters. Genes with an adjusted p-value of <0.05 and a log fold change >1.0 are included in this set. EntrezGene identifiers or sequence identifiers were converted to MGI identifiers. Genes that could not be converted were omitted. If a gene was represented more than once, the largest fold-change was chosen.
Authors:
Jose A Regla-Nava, Jose L Nieto-Torres, Jose M Jimenez-Guardeño, Raul Fernandez-Delgado, Craig Fett, Carlos Castaño-RodrÃguez, Stanley Perlman, Luis Enjuanes, Marta L DeDiego
Differential gene expression in nucleus accumbens somatostatin interneurons_cocaine_mice_pvalue
Description:
To characterize transcriptional alterations that cocaine induces in these cells, we perform cell type-specific RNA-sequencing on FACS-isolated nuclei of somatostatin interneurons and identified 1100 DETs enriched for processes related to neural plasticity. To profile the entire (non poly-A selected) transcriptome of NAc somatostatin interneurons, we generated a transgenic reporter line (SST-TLG498 mice) to label the nuclei of these cells with a modified form of EGFP that is retained in the nuclear membrane (EGFP-F)22, enabling their isolation from NAc dissections using FACS. We succeeded in FACS-isolating nuclei suitable for RNA-sequencing from individual SST-TLG498 mice. We proceeded with differential expression analysis of the RNA-sequencing data to identify differentially expressed transcripts (DETs) in NAc somatostatin interneurons in response to repeated cocaine exposure: 778 transcripts were upregulated by cocaine and 322 were downregulated.
Authors:
Efrain A Ribeiro, Marine Salery, Joseph R Scarpa, Erin S Calipari, Peter J Hamilton, Stacy M Ku, Hope Kronman, Immanuel Purushothaman, Barbara Juarez, Mitra Heshmati, Marie Doyle, Casey Lardner, Dominicka Burek, Ana Strat, Stephen Pirpinias, Ezekiell Mouzon, Ming-Hu Han, Rachael L Neve, Rosemary C Bagot, Andrew Kasarskis, Ja Wook Koo, Eric J Nestler
Differentially expressed genes in male cerebellum from microarray analysis. MeHg stands for Methyl Mercury. after 1.99 mg/kg of MeHg MeHg was compared against NCM, OCs, PCBs ant PTU via differential expression.
Authors:
Padhi BK, Pelletier G, Williams A, Berndt-Weis L, Yauk C, Bowers WJ, Chu I
Differentially expressed genes in male cerebellum from microarray analysis. OC stands for Organochlorine Pesticides. Differential expression of OCs were compared against differential expression of MeHg, NCM, PCBs and PTU.
Authors:
Padhi BK, Pelletier G, Williams A, Berndt-Weis L, Yauk C, Bowers WJ, Chu I
Differentially expressed genes in male cerebellum from microarray analysis. PTU stands for Propylthiouracil. Differential expression of PTU were compared against differential expression of MeHg, NCM, PCBs and OCs. PTUs were used as a positive control
Authors:
Padhi BK, Pelletier G, Williams A, Berndt-Weis L, Yauk C, Bowers WJ, Chu I
Differentially expressed genes in male cerebellum from microarray analysis. PCB stands for polychlorinated biphenyls. Differential expression of PCB were compared against differential expression of MeHg, NCM, OCs and PTU.
Authors:
Padhi BK, Pelletier G, Williams A, Berndt-Weis L, Yauk C, Bowers WJ, Chu I
Differentially expressed genes in female cerebellum from microarray analysis. NCM stands for northern contaminant mixture. Differential expression of NCMs were compared against MeHg, PCBs, OCs and PTU
Authors:
Padhi BK, Pelletier G, Williams A, Berndt-Weis L, Yauk C, Bowers WJ, Chu I
Differentially expressed genes in female cerebellum from microarray analysis. OC stands for Organochlorine Pesticides. Differential expression of OCs were compared against differential expression of MeHg, NCM, PCBs and PTU.
Authors:
Padhi BK, Pelletier G, Williams A, Berndt-Weis L, Yauk C, Bowers WJ, Chu I
Differentially expressed genes in female cerebellum from microarray analysis. PCB stands for polychlorinated biphenyls. Differential expression of PCBs were compared against differential expression of MeHg, NCM, OCs and PTU.
Authors:
Padhi BK, Pelletier G, Williams A, Berndt-Weis L, Yauk C, Bowers WJ, Chu I
Differentially expressed genes in female cerebellum from microarray analysis. PTU stands for propylthiouracil. Differential expression of PTUs were compared against differential expression of MeHg, NCM, PCBs and OCs.
Authors:
Padhi BK, Pelletier G, Williams A, Berndt-Weis L, Yauk C, Bowers WJ, Chu I
Whole Brain Gene Expression Correlates for ACTI15_SAL measured in BXD RI Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The ACTI15_SAL measures Distance traveled (cm) during the third five minute bin after saline under the domain Ethanol. 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
Hippocampus Gene Expression Correlates for LM_CUE_ACTIVITY measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The LM_CUE_ACTIVITY measures Activity in altered context during presentation of cue 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
Hippocampus Gene Expression Correlates for LM_CUE_SUPPRESS measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The LM_CUE_SUPPRESS measures Suppression of activity in altered context 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
Whole Brain Gene Expression Correlates for NEINVCOUNT30 measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The NEINVCOUNT30 measures Novel environment rears 15-30 min in the center 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
Whole Brain Gene Expression Correlates for NOVEL_VCOUNT_1 measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The NOVEL_VCOUNT_1 measures Open Field Inovel TOTAL rears in the center under the domain Morphine. 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
Whole Brain Gene Expression Correlates for ST_MAX_85 measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The ST_MAX_85 measures Maximum startle response to 85 db 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
Whole Brain Gene Expression Correlates for ACTI10_SAL measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The ACTI10_SAL measures Distance traveled (cm) during the second five minute bin after saline under the domain Ethanol. 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
Whole Brain Gene Expression Correlates for ACTI10_SAL measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The ACTI10_SAL measures Distance traveled (cm) during the second five minute bin after saline under the domain Ethanol. 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
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