Gene expression correlation with morphine response in BXD mice
Description:
Dataset represents the correlation between gene expression in prefrontal cortex from GeneNetwork dataset DOD BXD PFC GWI CTL RNA-seq ComB (Dec19) TPM Log2 with GeneNetwork dataset for BXD mice labeled as: Central nervous system, pharmacology, behavior: Morphine response (50 mg/kg ip), locomotion (open field) from 45-60 min after injection in an activity chamber for males [cm] with peak at Chr10: 5.636905. Data shown here are p-adjusted values < 0.05.
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 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
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
Chronic cocaine - Cocaine-paired (conditioned place preference) vs. Control (saline or cocaine-non-paired) DNA microarray All genes on microarray presented After the pre-conditioning phase where animals were allowed access to either compartment for 15 minutes for 4 consecutive days, the conditioning phase for the cocaine-paired groups and cocaine non-paired groups began, consisting of eight subsequent daily sessions. For both groups, cocaine (10 mg / kg) or saline injections were administered on alternate days. For the cocaine-paired groups, rats were immediately placed in one of the two compartments for 30 min with the door in place restricting a z transformation followed by z test and anova followed by Student-Newman-Keuls' post hoc test. Gene expression profile was assessed 24 h after the last conditioning session that corresponded to 48 h after last cocaine exposure, when drug has been eliminated from the body and transient transcriptional changes are likely to be minimal. Therefore, changes in gene expression at this time-point are likely to reflect longer lasting adaptations that may account for maintenance of cocaine-induced memories. The complete lists of normalized gene expression values for the hippocampus of saline-treated, cocaine non-paired and cocaine-paired groups are presented. Analyses revealed that 214 transcripts were differentially regulated in the hippocampus of cocaine-paired rats vs. non-paired and saline-treated controls. Cocaine-induced conditioned place preference caused significant increases in the expression of 151 genes and caused decreases in the expression of 63 genes. (NIF Table ID 130.1 [83])
Authors:
Krasnova IN, Li SM, Wood WH, McCoy MT, Prabhu VV, Becker KG, Katz JL, Cadet JL
Chronic cocaine - Cocaine-paired (conditioned place preference) vs. Control (saline or cocaine-non-paired) DNA microarray All genes on microarray presented After the pre-conditioning phase where animals were allowed access to either compartment for 15 minutes for 4 consecutive days, the conditioning phase for the cocaine-paired groups and cocaine non-paired groups began, consisting of eight subsequent daily sessions. For both groups, cocaine (10 mg / kg) or saline injections were administered on alternate days. For the cocaine-paired groups, rats were immediately placed in one of the two compartments for 30 min with the door in place restricting a z transformation followed by z test and anova followed by Student-Newman-Keuls' post hoc test. Gene expression profile was assessed 24 h after the last conditioning session that corresponded to 48 h after last cocaine exposure, when drug has been eliminated from the body and transient transcriptional changes are likely to be minimal. Therefore, changes in gene expression at this time-point are likely to reflect longer lasting adaptations that may account for maintenance of cocaine-induced memories. The complete lists of normalized gene expression values for the frontal cortex of saline-treated, cocaine non-paired and cocaine-paired groups are presented. Differences in the expression of 39 transcripts in the frontal cortex were related to the conditioned place preference paradigm. These include increases in the level of 22 genes and decreases in 17 genes. (NIF Table ID 130.3 [83.5])
Authors:
Krasnova IN, Li SM, Wood WH, McCoy MT, Prabhu VV, Becker KG, Katz JL, Cadet JL
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