Data from GEO GSE194368 and analyzed using GEO2R, only top gene shown. Authors identified transcriptional adaptations of GR signaling in the amygdala of humans with OUD. Thus, GRs, their coregulators and downstream systems may represent viable therapeutic targets to treat the “stress side” of OUD.
Authors:
Stephanie A Carmack, Janaina C M Vendruscolo, M Adrienne McGinn, Jorge Miranda-Barrientos, Vez Repunte-Canonigo, Gabriel D Bosse, Daniele Mercatelli, Federico M Giorgi, Yu Fu, Anthony J Hinrich, Francine M Jodelka, Karen Ling, Robert O Messing, Randall T Peterson, Frank Rigo, Scott Edwards, Pietro P Sanna, Marisela Morales, Michelle L Hastings, George F Koob, Leandro F Vendruscolo
Hippocampus Gene Expression Correlates for NEPDIST60 measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The NEPDIST60 measures Novel environment locomotion (cm) 45-60 min in the periphery 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
Hippocampus Gene Expression Correlates for NEPDIST60 measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The NEPDIST60 measures Novel environment locomotion (cm) 45-60 min in the periphery under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Hippocampus Gene Expression Correlates for NEPDIST60 measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The NEPDIST60 measures Novel environment locomotion (cm) 45-60 min in the periphery under the domain Cocaine. The correlates were thresholded at a p-value of less than 0.001.
QTL for METH responses for climbing on Chr5 at D5Byu4 (129.78 Mbp , Build 37)
Description:
METH responses for climbing spans 104.78 - 154.78 Mbp (NCBI Build 37) on Chr5. 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 climbing on Chr5 at Ache (142.47 Mbp , Build 37)
Description:
METH responses for climbing spans 117.47 - 167.47 Mbp (NCBI Build 37) on Chr5. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Genes associated (p < .05) with the genetic predisposition to cocaine dependence in African Americans (n > 3000). All individuals reported using cocaine and analyses utilized a classic case-control design and a MAGMA gene-based test: see Huggett & Stallings, 2020 Journal of Neuroscience (in review) for more details.
Genes associated (p < .05) with the genetic predisposition to cocaine dependence in African Americans (n > 3000). All individuals reported using cocaine and analyses utilized a classic case-control design and a MAGMA gene-based test: see Huggett & Stallings, 2020 Journal of Neuroscience (in review) for more details.
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
Gene expression in 212,713 ventral midbrain single nuclei from 95 individuals with history of opioid misuse, and individuals without drug exposure. Chronic exposure to opioids was not associated with change in proportions of glial and neuronal subtypes, however glial transcriptomes were broadly altered, involving 9.5 - 6.2% of expressed genes within microglia, oligodendrocytes, and astrocytes. Genes associated with activation of the immune response including interferon, NFkB signaling, and cell motility pathways were upregulated, contrasting with down-regulated expression of synaptic signaling and plasticity genes in ventral midbrain non-dopaminergic neurons. Ventral midbrain transcriptomic reprogramming in the context of chronic opioid exposure included 325 genes that previous genome-wide studies had linked to risk of substance use traits in the broader population.
Authors:
Julong Wei, Tova Y Lambert, Aditi Valada, Nikhil Patel, Kellie Walker, Jayna Lenders, Carl J Schmidt, Marina Iskhakova, Adnan Alazizi, Henriette Mair-Meijers, Deborah C Mash, Francesca Luca, Roger Pique-Regi, Michael J Bannon, Schahram Akbarian
Authors interrogated the effects of opioid overdose on the brain using ChIP-seq to quantify patterns of H3K27 acetylation in dorsolateral prefrontal cortical neurons isolated from 51 opioid-overdose cases and 51 accidental death controls.Authors use the term plexus to refer to the collection of regulatory elements that physically contact the gene promoter. Plexi are derived from DLPFC promoter-capture Hi-C. Here, they used convergence analysis to identify genetic loci and target genes that have an overabundance of opioid case Variant Enhancer Loci, VELs. The strategy identifies single elements in a gene plexus altered across multiple cases, multiple elements altered within a single case, multiple elements altered across multiple cases, and intermediate patterns. This approach takes into account the differing number of elements contained in each gene’s plexus and their activity to identify genes with the most significant accumulation of VELs. Results displaed include GeneName and -log10pvalue.
Authors:
Olivia Corradin, Richard Sallari, An T Hoang, Bibi S Kassim, Gabriella Ben Hutta, Lizette Cuoto, Bryan C Quach, Katreya Lovrenert, Cameron Hays, Berkley E Gryder, Marina Iskhakova, Hannah Cates, Yanwei Song, Cynthia F Bartels, Dana B Hancock, Deborah C Mash, Eric O Johnson, Schahram Akbarian, Peter C Scacheri
GeneWeaver