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
Differential expression analysis for short access cocaine self-admin (coke vs saline) in C57 male mice using data from Walker et al. 2018 Biological Psychiatry.
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
Drug NaĂŻve DO mice were tested for open field, light dark, hole board, novelty place preference before collecting the striatum. RNA-Seq data was analyzed with WGCNA using a soft thresholding power of 3 selected using the WGCNA scale-free topology R2 threshold of 0.9, signed network with a minimum module size of 30, correlation type is bicor, used numeric labels.
Genes identified as expressed lower (down) in the AJ strain than in the CAST strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed lower (down) in the AJ strain than in the CAST strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed higher (up) in the AJ strain than in the NOD strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed higher (up) in the AJ strain than in the NZO strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed higher (up) in the AJ strain than in the NOD strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed higher (up) in the AJ strain than in the NZO strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed lower (down) in the AJ strain than in the CAST strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed lower (down) in the AJ strain than in the CAST strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed higher (up) in the AJ strain than in the S129 strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed higher (up) in the AJ strain than in the S129 strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
QTL for ethanol withdrawal on Chr13 at D13Ncvs35 (71.29 Mbp , Build 37)
Description:
ethanol withdrawal spans 46.29 - 96.29 Mbp (NCBI Build 37) on Chr13. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Genes identified as expressed lower (down) in the AJ strain than in the CAST strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Genes identified as expressed lower (down) in the AJ strain than in the CAST strain. Differentially expressed genes had a Q-value < 0.05 following the Benjamini-Hochberg methodology for false discovery rates in the limma+voom pipeline within edgeR. Q-value is reported from the topTable function.
Differentially expressed geens in the central amygdala (CeA) of male Sprague-Dawley rats (300-350 g prior to surgery, 325-375 g at start of self-administration) on day 2 following methamphetamine withdrawal. Gene Expression was evaluated via RNA-seq. Data taken from Supplementary Table S2. Values presented are adjusted p-values. Data available from GEO with accession number GSE111243."
Authors:
Hannah M Cates, Xuan Li, Immanuel Purushothaman, Pamela J Kennedy, Li Shen, Yavin Shaham, Eric J Nestler
Differentially expressed geens in the central amygdala (CeA) of male Sprague-Dawley rats (300-350 g prior to surgery, 325-375 g at start of self-administration) on day 35 following methamphetamine withdrawal. Gene Expression was evaluated via RNA-seq. Data taken from Supplementary Table S2. Values presented are adjusted p-values. Data available from GEO with accession number GSE111243."
Authors:
Hannah M Cates, Xuan Li, Immanuel Purushothaman, Pamela J Kennedy, Li Shen, Yavin Shaham, Eric J Nestler
Alcohol transcriptome changes in mice microglia total homogenate p-value
Description:
Microglia are fundamentally important immune cells within the central nervous system (CNS) that respond to environmental challenges to maintain normal physiological processes. Alterations in steady-state cellular function and over-activation of microglia can facilitate the initiation and progression of neuropathological conditions such as Alzheimer’s disease, Multiple Sclerosis, and Major Depressive Disorder. Alcohol consumption disrupts signaling pathways including both innate and adaptive immune responses that are necessary for CNS homeostasis. Coordinate expression of these genes is not ascertained from an admixture of CNS cell-types, underscoring the importance of examining isolated cellular populations to reveal systematic gene expression changes arising from mature microglia. Unbiased RNA-Seq profiling was used to identify gene expression changes in isolated prefrontal cortical microglia in response to recurring bouts of voluntary alcohol drinking behavior. The voluntary ethanol paradigm utilizes long-term consumption ethanol that results in escalated alcohol intake and altered cortical plasticity that is seen in humans. Gene coexpression analysis identified a coordinately regulated group of genes, unique to microglia, that collectively are associated with alcohol consumption. Genes within this group are involved in toll-like receptor signaling and transforming growth factor beta signaling. Network connectivity of this group identified Siglech as a putative hub gene and highlighted the potential importance of proteases in the microglial response to chronic ethanol. In conclusion, we identified a distinctive microglial gene expression signature for neuroimmune responses related to alcohol consumption that provides valuable insight into microglia-specific changes underlying the development of substance abuse, and possibly other CNS disorders.
Authors:
Gizelle M McCarthy, Sean P Farris, Yuri A Blednov, R Adron Harris, R Dayne Mayfield
Genes associated with Mus musculus that interact with the MeSH term 'Acetaminophen' (D000082). Incorporates data from 2 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Authors:
None
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