Hippocampus Gene Expression Correlates for MDMA_ACT_SAL_1 measured in BXD RI Females & Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The MDMA_ACT_SAL_1 measures Locomotor activity of mice on Day 1 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
Hippocampus Gene Expression Correlates for MDMA_ACT_SAL_1 measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The MDMA_ACT_SAL_1 measures Locomotor activity of mice on Day 1 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
Whole Brain Gene Expression Correlates for MDMA_ACT_SAL_1 measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The MDMA_ACT_SAL_1 measures Locomotor activity of mice on Day 1 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
A list of genes whose transcript abundance in the PFC changed significantly 4 hours after an acute dose of ethanol (1.8 g/kg). This list was generated using Fisher's Combined Probability test to analyze saline vs ethanol S-scores across B6 and D2 inbred strains (n=3) and 27 BXD RI lines (n=1). Statistical significance was determined using 1,000 permutations of S-score data and selecting for probe-sets with q-values < 0.05. Aaron Wolen 5-26-10.
Authors:
Wolen AR, Phillips CA, Langston MA, Putman AH, Vorster PJ, Bruce NA, York TP, Williams RW, Miles MF
None - Basal gene expression profiles between C57BL/6J, DBA/2J, 129P3/J, and SWR/J strains DNA microarray Change in gene expression Two-way analysis of variance (ANOVA). 3,457 probe sets (corresponded to 2,870 different transcripts) with significant inter-strain differences (differ by at least 1.2-fold) - False discovery rate [FDR] < 1%, , rank > 3. Such a large disparity in the mouse striatal transcriptome was estimated by comparing nine array replicates prepared per strain from all of the treatment groups. More than half of the identified probe sets exhibited markedly significant results (1,735 with rank > 7). (NIF Method ID 84.1)
Authors:
Korostynski M, Piechota M, Kaminska D, Solecki W, Przewlocki R
Top 200 genes enriched in Astrocytes compared to neurons, endothelial cells, microglia, myelinating oligodendrocytes, newly formed oligodendrocytes and OPCs.
Authors:
Zhang Y, Chen K, Sloan SA, Bennett ML, Scholze AR, O\'Keeffe S, Phatnani HP, Guarnieri P, Caneda C, Ruderisch N, Deng S, Liddelow SA, Zhang C, Daneman R, Maniatis T, Barres BA, Wu JQ
Here, female High Drinking in the Dark (HDID) mice were stereotaxically injected with 0.5uL rAAV2/5-CMV-Cre-GFP and 0.5uL rAAV2-hSyn-DIO-hM3Dq-mCherry bilaterally into the NAc. A Drinking in the Dark (DID) experiment lasting 6 weeks was carried out with 2 fluid groups (water or ethanol) and 2 treatment groups (VEH/VEH/VEH or VEH/CNO/VEH). Mice were serially treated with vehicle prior to DID during week 1 to establish baseline drinking, CNO (1mg/kg) during weeks 2-5 to measure the effects of chronic treatment, and then mice were treated with vehicle again during week 6 to determine if there were any lasting effects of chronic CNO treatment. This gene set comprises 2,377 genes that were differentially expressed in the nucleus accumbens of ethanol drinking HDID mice treated with CNO as compared to the water drinking and vehicle treated control group.
Authors:
Darya Y. Pozhidayeva, Sean P. Farris, Calla M. Goeke, Evan J. Firsick, Kayla G. Townsley, Marina Guizzetti, and Angela R. Ozburn
Genes differentially expressed between methamphetamine low drink (MALDR) and methamphetamine high drink (MAHDR) mice from Belknap et al. (2013) , p < 0.01. Data reported in Table S14 for comparison with genes in the present study. Values presented are p-values.
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
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
Chronic alcohol in mice DEG in astrocytes microglia p-value
Description:
Astrocytes play critical roles in central nervous system (CNS) homeostasis and are implicated in the pathogenesis of neurological and psychiatric conditions, including drug dependence. Little is known about the effects of chronic ethanol consumption on astrocyte gene expression. To address this gap in knowledge, we performed transcriptome-wide RNA sequencing of astrocytes isolated from the prefrontal cortex (PFC) of mice following chronic ethanol consumption. Differential expression analysis revealed ethanol-induced changes unique to astrocytes that were not identified in total homogenate preparations. Astrocyte-specific gene expression revealed calcium-related signaling and regulation of extracellular matrix genes as responses to chronic ethanol use. These findings emphasize the importance of investigating expression changes in specific cellular populations to define molecular consequences of chronic ethanol consumption in mammalian brain. Reported are differentially expressed genes in total homogenate after EOD (p < 0.05).
Authors:
Emma K Erickson, Sean P Farris, Yuri A Blednov, R Dayne Mayfield, R Adron Harris
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
Differential gene expression in the nucleus accumbens of WT vs SERT Met172 mice after chronic cocaine treatment_FDR
Description:
To elucidate 5-HT transporter (SERT)-specific contributions to cocaine action, we evaluated cocaine effects in the SERT Met172 knock-in mouse, which expresses a SERT coding substitution that eliminates high-affinity cocaine recognition. We measured the effects of SERT Met172 on cocaine antagonism of 5-HT re-uptake using ex vivo synaptosome preparations and in vivo microdialysis. We assessed SERT dependence of cocaine actions behaviourally through acute and chronic locomotor activation, sensitization, conditioned place preference (CPP) and oral cocaine consumption.
Authors:
Linda D Simmler, Allison M J Anacker, Michael H Levin, Nina M Vaswani, Paul J Gresch, Alex G Nackenoff, Noelle C Anastasio, Sonja J Stutz, Kathryn A Cunningham, Jing Wang, Bing Zhang, L Keith Henry, Adele Stewart, Jeremy Veenstra-VanderWeele, Randy D Blakely
Differential gene expression in the prelimbic cortex of WT and SERT Met172 mice after chronic cocaine treatment_FDR
Description:
To elucidate 5-HT transporter (SERT)-specific contributions to cocaine action, we evaluated cocaine effects in the SERT Met172 knock-in mouse, which expresses a SERT coding substitution that eliminates high-affinity cocaine recognition. We measured the effects of SERT Met172 on cocaine antagonism of 5-HT re-uptake using ex vivo synaptosome preparations and in vivo microdialysis. We assessed SERT dependence of cocaine actions behaviourally through acute and chronic locomotor activation, sensitization, conditioned place preference (CPP) and oral cocaine consumption.
Authors:
Linda D Simmler, Allison M J Anacker, Michael H Levin, Nina M Vaswani, Paul J Gresch, Alex G Nackenoff, Noelle C Anastasio, Sonja J Stutz, Kathryn A Cunningham, Jing Wang, Bing Zhang, L Keith Henry, Adele Stewart, Jeremy Veenstra-VanderWeele, Randy D Blakely
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