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.
Affymetrix oligonucleotide arrays to assess gene expression in brains of mice selectively bred for differences in acute functional tolerance to an incoordinating effect of ethanol (HAFT mice, high acute functional tolerance; LAFT mice, low acute functional tolerance)
Hippocampus Gene Expression Correlates for LM_PAIR3 measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The LM_PAIR3 measures Activity during 3rd tone shock pairing 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
Striatum Gene Expression Correlates for ST_PCT_PPI_80 measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The ST_PCT_PPI_80 measures Prepulse inhibition at 80db 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
Striatum Gene Expression Correlates for ST_PCT_PPI_85 measured in BXD RI Females obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The ST_PCT_PPI_85 measures Prepulse inhibition at 85db 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
Striatum Gene Expression Correlates for ST_PCT_STARTLE_80 measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The ST_PCT_STARTLE_80 measures Acoustic Startle Response Percentage of maximum startle response at 80 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
Striatum Gene Expression Correlates for ST_PCT_STARTLE_85 measured in BXD RI Females obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The ST_PCT_STARTLE_85 measures Acoustic Startle Response Percentage of maximum response at 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
Cerebellum Gene Expression Correlates for TAILCLIP_LAT_SEC measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The TAILCLIP_LAT_SEC measures Mechanical Nociception - Tail Clip Test under the domain Pain. 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 MDMA_ACT_MDA_1 measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The MDMA_ACT_MDA_1 measures Locomotor response of 10 mg/kg MDMA injected on Day 2 under the domain MDMA. 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 VOCA_THRESHOLD measured in BXD RI Females & Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The VOCA_THRESHOLD measures Vocalization Threshold - shock intensity (mA) under the domain Stress Vocalization. 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 VOCA_THRESHOLD measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The VOCA_THRESHOLD measures Vocalization Threshold - shock intensity (mA) under the domain Stress Vocalization. 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 VOCA_THRESHOLD measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The VOCA_THRESHOLD measures Vocalization Threshold - shock intensity (mA) under the domain Stress Vocalization. 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
Renthal W, Kumar A, Xiao G, Wilkinson M, Covington HE 3rd, Maze I, Sikder D, Robison AJ, LaPlant Q, Dietz DM, Russo SJ, Vialou V, Chakravarty S, Kodadek TJ, Stack A, Kabbaj M, Nestler EJ
QTL for high-dose ethanol actions on Chr14 at D14Mit1 (5.65 Mbp , Build 37)
Description:
high-dose ethanol actions spans 0.00 - 30.65 Mbp (NCBI Build 37) on Chr14. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Erwin VG, Markel PD, Johnson TE, Gehle VM, Jones BC
QTL for METH responses for chewing on Chr14 at D14Mit54 (23.48 Mbp , Build 37)
Description:
METH responses for chewing spans 0.00 - 48.48 Mbp (NCBI Build 37) on Chr14. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for METH responses for body temperature on Chr14 at Glud (26.89 Mbp , Build 37)
Description:
METH responses for body temperature spans 1.89 - 51.89 Mbp (NCBI Build 37) on Chr14. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for METH responses for home cage activity on Chr14 at Mtv11 (27.12 Mbp , Build 37)
Description:
METH responses for home cage activity spans 2.12 - 52.12 Mbp (NCBI Build 37) on Chr14. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for METH responses for home cage activity on Chr14 at Ms15-7 (28.18 Mbp , Build 37)
Description:
METH responses for home cage activity spans 3.18 - 53.18 Mbp (NCBI Build 37) on Chr14. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for cocaine seizure on Chr14 at NA (38.23 Mbp , Build 37)
Description:
cocaine seizure spans 13.23 - 63.23 Mbp (NCBI Build 37) on Chr14. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
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