Microglia depletion and alcohol gene expression logFC
Description:
Alcohol abuse induces changes in microglia morphology and immune function, but whether microglia initiate or simply amplify the harmful effects of alcohol exposure is still a matter of debate. Here, we determine microglia function in acute and voluntary drinking behaviors using a colony-stimulating factor 1 receptor inhibitor (PLX5622). We show that microglia depletion does not alter the sedative or hypnotic effects of acute intoxication. Microglia depletion also does not change the escalation or maintenance of chronic voluntary alcohol consumption. Transcriptomic analysis revealed that although many immune genes have been implicated in alcohol abuse, down regulation of microglia genes does not necessitate changes in alcohol intake. Instead, microglia depletion and chronic alcohol result in compensatory upregulation of alcohol-responsive, reactive astrocyte genes, indicating astrocytes may play a role in regulation of these alcohol behaviors. Taken together, our behavioral and transcriptional data indicate that microglia are not theprimary effector cell responsible for regulation of acute and voluntary alcohol behaviors. Because microglia depletion did not regulate acute or voluntary alcohol behaviors, we hypothesized that these doses were insufficient to activate microglia and recruit them to an effector phenotype. Therefore, we used a model of repeated immune activation using polyinosinic:polycytidylic acid
We investigated the role of microglia in a mouse model of alcohol dependence using a colony stimulating factor 1 receptor inhibitor (PLX5622) to deplete microglia and a chronic intermittent ethanol vapor two-bottle choice drinking procedure. Additionally, we examined anxiety-like behavior during withdrawal. We then analyzed synaptic neuroadaptations in the central nucleus of the amygdala (CeA) and gene expression changes in the medial prefrontal cortex (mPFC) and CeA from the same animals used for behavioral studies.
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 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 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 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 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 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.
Alcohol interaction of dependence and MG depletion the medial prefrontal cortex q-value
Description:
We investigated the role of microglia in a mouse model of alcohol dependence using a colony stimulating factor 1 receptor inhibitor (PLX5622) to deplete microglia and a chronic intermittent ethanol vapor two-bottle choice drinking procedure. Additionally, we examined anxiety-like behavior during withdrawal. We then analyzed synaptic neuroadaptations in the central nucleus of the amygdala (CeA) and gene expression changes in the medial prefrontal cortex (mPFC) and CeA from the same animals used for behavioral studies.
H3 dopaminylation at glutamine 5 (H3Q5dop) plays a critical role in heroin-mediated transcriptional plasticity in midbrain regions, particularly the VTA. In rats undergoing abstinence from heroin self-administration (SA), we found acute and persistent accumulation of H3Q5dop in VTA. Attenuation of H3Q5dop during abstinence induced persistent changes in gene expression programs associated with neuronal signaling and dopaminergic function in heroin abstinence and led to reduced heroin-seeking behavior. Interestingly, the observed changes in molecular pathways after heroin SA showed significant yet reversed overlap with the same genes altered in cocaine SA.
Authors:
Sasha L Fulton, Swarup Mitra, Ashley E Lepack, Jennifer A Martin, Andrew F Stewart, Jacob Converse, Mason Hochstetler, David M Dietz, Ian Maze
Genes identified as expressed higher (up) in the AJ strain than in the AJ 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 AJ 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 AJ 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 AJ 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.
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
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
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