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.
Alcohol dependence in 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.
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
This gene set comprises 239 genes that are differentially expressed within each of five brain regions (amygdala, hippocampus, nucleus accumbens, prefrontal cortex and ventral tegmental area) when chronic nicotine treatment is administered to C57BL/6J mice only. Background: Studies involving use of chronic nicotine treatment identify unique nicotine addiction genes and the biological processes they control in B6 and C3 mice. Results are obtained using gene expression profiling and gene ontology.
Authors:
Wang J, Gutala R, Hwang YY, Kim JM, Konu O, Ma JZ, Li MD
This gene set comprises 66 genes that are upregulated within each of five brain regions (amygdale, hippocampus, nucleus accumbens, prefrontal cortex and ventral tegmental area) when chronic nicotine treatment is administered to B6 mice only. Background: Studies involving chronic nicotine treatment identify unique nicotine addiction genes and the biological processes they mediate in C3 and B6 mice. Results are obtained using gene expression profiling via cDNA microarrays and gene ontology.
Authors:
Wang J, Gutala R, Hwang YY, Kim JM, Konu O, Ma JZ, Li MD
Neocortex Gene Expression Correlates for AMCNT15 measured in BXD RI Females & Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The AMCNT15 measures Morphine photocell counts minutes 0-15 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
Neocortex Gene Expression Correlates for AMCNT15 measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The AMCNT15 measures Morphine photocell counts minutes 0-15 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
Striatum Gene Expression Correlates for ENTRIES_CLOSED measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The ENTRIES_CLOSED measures Number of entries into closed arms of plus maze 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
Striatum Gene Expression Correlates for ENTRIES_OPEN measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The ENTRIES_OPEN measures Number of entries into open arms of plus maze under the domain Ethanol. The correlates were thresholded at a p-value of less than 0.001.
Hippocampus Gene Expression Correlates for SPD_TIMEDOWEL0SEC measured in BXD RI Females & Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The SPD_TIMEDOWEL0SEC measures Dowel Test - Time 0 Sec under the domain Porsolt. 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 SPD_TIMEDOWEL0SEC measured in BXD RI Females & Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The SPD_TIMEDOWEL0SEC measures Dowel Test - Time 0 Sec under the domain Porsolt. 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
Striatum Gene Expression Correlates for PCT_ENTRIES_CLOSED measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The PCT_ENTRIES_CLOSED measures Percentage of entries into closed arms of plus maze under the domain Porsolt. 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
F2 mice from a hybrid cross of C57BL/6J and FVB/NJ had heightened consumption of EtOH in 2 bottle, water versus ethanol, choice, with accending ethanol levels. Chromosome 11 had multiple suggestive markers, with LOD scores reflecting both additive and dominance variation taken together, as shown in Fig. 5.
Authors:
Phillips TJ, Reed C, Burkhart-Kasch S, Li N, Hitzemann R, Yu CH, Brown LL, Helms ML, Crabbe JC, Belknap JK
Heterozygote mice from a hybrid cross of C57BL/6J and FVB/NJ had heightened EtOH consumption, preference or blood EtOH concentration compared to either homozygous groups. The magnitude of dominant deviation on Chr. 11, as noted in Fig. 9, was measured after a drinking in the dark paradigm, 24hr two-bottle-choice and subsequent blood ethanol concentration measurement.
Authors:
Phillips TJ, Reed C, Burkhart-Kasch S, Li N, Hitzemann R, Yu CH, Brown LL, Helms ML, Crabbe JC, Belknap JK
Striatum Gene Expression Correlates for ENTRIES_CLOSED measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The ENTRIES_CLOSED measures Number of entries into closed arms of plus maze under the domain Ethanol. The correlates were thresholded at a p-value of less than 0.001.
All genes listed were differentially expressed between selectively bred HAP and LAP mice using both normalization methods (RMA and MAS5.0), using two different statistical analyses (permutation and t-test noise distribution), and in both the original and replicate lines at a p value of 0.20 or less and they also had a significant (p < 0.05) or suggestive (0.05 < p < 0.10) eQTL that was located within a bQTL for alcohol preference (2-bottle choice); from Saba et al., 2006
Authors:
Saba L, Bhave SV, Grahame N, Bice P, Lapadat R, Belknap J, Hoffman PL, Tabakoff B
Genes with a mean fold change > 1.5 or < 0.7 were selected and annotated. Values are taken from microarray analysis and represent mean ratios of alcoholic cases compared with matched control cases(n = 6). P values were from t-test; from Flatscher-Bader et al., 2005
Authors:
Flatscher-Bader T, van der Brug M, Hwang JW, Gochee PA, Matsumoto I, Niwa S, Wilce PA
QTL for chronic alcohol withdrawal severity on Chr11 at D11Mit4 (58.98 Mbp , Build 37)
Description:
chronic alcohol withdrawal severity spans 33.98 - 83.98 Mbp (NCBI Build 37) on Chr11. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Bergeson SE, Kyle Warren R, Crabbe JC, Metten P, Gene Erwin V, Belknap JK
QTL for alcohol preference locus on Chr11 at NA (70.38 Mbp , Build 37)
Description:
alcohol preference locus spans 45.38 - 95.38 Mbp (NCBI Build 37) on Chr11. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Gill K, Desaulniers N, Desjardins P, Lake K
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