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Tier I

1680

GS128591: Average rotarod training latency Chr# 5

Tier IV

19215

GS406229: cc coca diffcoexp universe

Tier IV

1058

GS407020: DO Striatum WGCNA blue module

Tier III

3091

GS407750: Glial gene expression associated with alcohol dependence in mice in astrocytes q-value

Figure Label:	Alcohol DEG in mice in astrocytes q-value
Description:	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

Tier III

24063

GS407758: Microglial-specific transcriptome changes following chronic alcohol consumption in mice total homogenate p-value

Figure Label:	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

Tier III

26322

GS407879: Genes differentially expressed with Fentanyl in C57BL/6 J and A/J in nucleus accumbens by stain_qvalue

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351