Striatum Gene Expression Correlates for ACTI_DIFF_05 measured in BXD RI Females obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The ACTI_DIFF_05 measures Difference in distance traveled (cm) during the first five min (saline-ethanol) 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 ROTAETHA_TIME measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The ROTAETHA_TIME measures Mean time on rotarod following ethanol 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
Whole Brain Gene Expression Correlates for HAND_BASELINE measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The HAND_BASELINE measures Handling induced convulsion baseline under the domain Ethanol HIC. 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 NEINCOUNT60 measured in BXD RI Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The NEINCOUNT60 measures Novel environment locomotion (activity beam breaks) 45-60 min in the center under the domain Cocaine. 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 NEINDIST60 measured in BXD RI Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The NEINDIST60 measures Novel environment locomotion (cm) 45-60 min in the center under the domain Cocaine. 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 NX_VCOUNT_3 measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The NX_VCOUNT_3 measures Naloxone induced Morphine Withdrawal - TOTAL vertical activity counts in 15 minutes 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 NX_VCOUNT_3 measured in BXD RI Females obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The NX_VCOUNT_3 measures Naloxone induced Morphine Withdrawal - TOTAL vertical activity counts in 15 minutes 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
QTL for ethanol withdrawal on Chr15 at D15Ncvs19 (0.00 Mbp , Build 37)
Description:
ethanol withdrawal spans 0.00 - 25.00 Mbp (NCBI Build 37) on Chr15. 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 high-dose ethanol actions on Chr15 at D15Mit12 (12.77 Mbp , Build 37)
Description:
high-dose ethanol actions spans 0.00 - 37.77 Mbp (NCBI Build 37) on Chr15. 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
Transcriptome sequencing from the SCNs of mice (C57BL/6J) entrained for 4 weeks to 22 h and 24 h d maintained for a week in darkness, and then killed at CT4 for each mouse. Supplementary table 3: List of the genomic regions hypermethylated in ST and Score.
Authors:
Azzi A, Dallmann R, Casserly A, Rehrauer H, Patrignani A, Maier B, Kramer A, Brown SA
Transcriptome sequencing from the SCNs of mice (C57BL/6J) entrained for 4 weeks to 22 h and 24 h d maintained for a week in darkness, and then killed at CT4 for each mouse. Supplementary table 3: List of the genomic regions hypomethylated in ST and Score.
Authors:
Azzi A, Dallmann R, Casserly A, Rehrauer H, Patrignani A, Maier B, Kramer A, Brown SA
Chronic alcohol abuse alters the molecular structure and function of brain cells. Recent work suggests adaptations made by glial cells, such as astrocytes and microglia, regulate physiological and behavioral changes associated with addiction. Defining how alcohol dependence alters the transcriptome of different cell types is critical for developing the mechanistic hypotheses necessary for a nuanced understanding of cellular signaling in the alcohol-dependent brain. We performed RnA-sequencing on total homogenate and glial cell populations isolated from mouse prefrontal cortex (pfc) following chronic intermittent ethanol vapor exposure (cie). compared with total homogenate, we observed unique and robust gene expression changes in astrocytes and microglia in response to cie. Gene co-expression network analysis revealed biological pathways and hub genes associated with cie in astrocytes and microglia that may regulate alcohol-dependent phenotypes. Astrocyte identity and synaptic calcium signaling genes were enriched in alcohol-associated astrocyte networks, while tGf-β signaling and inflammatory response genes were disrupted by CIE treatment in microglia gene networks. Genes related to innate immune signaling, specifically interferon pathways, were consistently up-regulated across cie-exposed astrocytes, microglia, and total homogenate pfc tissue. This study illuminates the cell-specific effects of chronic alcohol exposure and provides novel molecular targets for studying alcohol dependence.
Authors:
Emma K Erickson, Yuri A Blednov, R Adron Harris, R Dayne Mayfield
Alcohol transcriptome changes in mice microglia 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
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