Neocortex Gene Expression Correlates for NOVEL_RATIO measured in BXD RI Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The NOVEL_RATIO measures Novel Open Field - locomotion in the periphery as a function of total locomotion. 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
Neocortex Gene Expression Correlates for OF_TOT_PERIM_DIST_PCT measured in BXD RI Females & Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The OF_TOT_PERIM_DIST_PCT measures Open Field -Total distance in the perimeter 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
alcohol preference 3 QTL 124.51 - 174.51 Mbp (NCBI Build 37) on Chr4. 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 related behavior on Chr4 at 34M15-SP6 (151.65 Mbp , Build 37)
Description:
cocaine related behavior spans 126.65 - 176.65 Mbp (NCBI Build 37) on Chr4. 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 ethanol conditioned taste aversion on Chr4 at D4Ncvs25 (151.65 Mbp , Build 37)
Description:
ethanol conditioned taste aversion spans 126.65 - 176.65 Mbp (NCBI Build 37) on Chr4. 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 Chr4 at Sac (151.65 Mbp , Build 37)
Description:
METH responses for climbing spans 126.65 - 176.65 Mbp (NCBI Build 37) on Chr4. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Ethanol induced LORR Chr# 4 rs3695715 (3649824) with right flanking marker rs3663950 (135285447) and left marker rs6279100 (155557887). This was mapped in 300 + (b6x129)F2 mice.
Using a computational approach binding sites for these transcription factors within the promoter regions of annotated genes in the mouse, rat, and human genomes were identified. Combining a robust search algorithm to identify discrete binding sites, a comparison of targets across species, and an analysis of binding site locations within promoter regions, allowed fro the identification of candidate genes that are strong CREB- or zif268 targets and are thus regulated by neural activity.
Genes that are differentially expressed in adult male C57BL/6J mice given acute cocaine vs. acute saline. Tissue was collected from the ventral tegmental area (VTA) of the brain. Gene expression was evaluated via RNA-seq, and differential gene expression was determined via linear regression (LR).D13 Values presented are p-values. Data taken from Supplementary Table 1. Data available from GEO with accession number GSE155313."
Authors:
Rianne R Campbell, Siwei Chen, Joy H Beardwood, Alberto J López, Lilyana V Pham, Ashley M Keiser, Jessica E Childs, Dina P Matheos, Vivek Swarup, Pierre Baldi, Marcelo A Wood
Alcohol transcriptome changes in mice microglia total homogenate log2FC
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
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
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
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
Analysis using RNA-seq of FACS-purified oligodendrocytes revealed a large cohort of morphine-regulated genes. In addition, to investigate cell-type-specific opioid responses, we performed single-cell RNA sequencing (scRNA-seq) of the nucleus accumbens of mice following acute morphine treatment. Differential expression analysis uncovered unique morphine-dependent transcriptional responses by oligodendrocytes and astrocytes.
Authors:
Denis Avey, Sumithra Sankararaman, Aldrin K Y Yim, Ruteja Barve, Jeffrey Milbrandt, Robi D Mitra
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