Transcriptional profiling of the rat nucleus accumbens after modest or high alcohol exposure

Morud, Julia; Ashouri, Arghavan; Larsson, Erik; Ericson, Mia; Söderpalm, Bo

doi:10.1371/journal.pone.0181084

Cited by 7 publications

(7 citation statements)

References 37 publications

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“…Alcohol-induced transcriptional changes in brain tissue are often mild, widespread, and both brain region- and time-specific (Melendez et al, 2012; Morud et al, 2017; Smith et al, 2016). We identified lasting changes in eight alternatively spliced transcripts – CG3558 −RB , CG9098 −RA , CG9098 −RB , Sdc −RK , Sec31 −RA , shi −RP , SREBP −RC , Stat92E −RH .…”

Section: Discussionmentioning

confidence: 99%

Alcohol Activates Scabrous-Notch to Influence Associated Memories

Petruccelli

Feyder

Ledru

et al. 2018

Neuron

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Summary: Drugs of abuse, like alcohol, modulate gene expression in reward circuits and consequently alter behavior. However, the in vivo cellular mechanisms through which alcohol induces lasting transcriptional changes are unclear. We show that Drosophila Notch/Su(H) signaling, and the secreted fibrinogen-related protein Scabrous, in mushroom body (MB) memory circuitry, is important for the enduring preference of cues associated with alcohol’s rewarding properties. Alcohol exposure affects Notch responsivity in the adult MB and alters Su(H) targeting at the dopamine-2-like receptor (Dop2R). Alcohol-cue training also caused lasting changes to the MB nuclear transcriptome, including changes in the alternative splicing of Dop2R and newly implicated transcripts like Stat92E. Together, our data suggest that alcohol-induced activation of the highly conserved Notch pathway and accompanying transcriptional responses in memory circuitry contribute to addiction. Ultimately this provides mechanistic insight into the etiology and pathophysiology of Alcohol Use Disorder.

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Section: Discussionmentioning

confidence: 99%

Alcohol Activates Scabrous-Notch to Influence Associated Memories

Petruccelli

Feyder

Ledru

et al. 2018

Neuron

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“…(4) While we randomly selected the mice for the RNA-Seq analysis, the small sample size in each group ( N = 4), could be prone to sampling bias. Previous work has shown robust results with a similar samples sizes [ 142 , 143 ]. However, for WGCNA, 16 samples are just above the recommended sample size and could have resulted in noise in the network construction.…”

Section: Discussionmentioning

confidence: 96%

The influence of adolescent nicotine exposure on ethanol intake and brain gene expression

et al. 2018

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Nicotine and alcohol are often co-abused. Adolescence is a vulnerable period for the initiation of both nicotine and alcohol use, which can lead to subsequent neurodevelopmental and behavioral alterations. It is possible that during this vulnerable period, use of one drug leads to neurobiological alterations that affect subsequent consumption of the other drug. The aim of the present study was to determine the effect of nicotine exposure during adolescence on ethanol intake, and the effect of these substances on brain gene expression. Forty-three adolescent female C57BL/6J mice were assigned to four groups. In the first phase of the experiment, adolescent mice (PND 36–41 days) were exposed to three bottles filled with water or nicotine (200 μg/ml) for 22 h a day and a single bottle of water 2 h a day for six days. In the second phase (PND 42–45 days), the 4-day Drinking-in-the-Dark paradigm consisting of access to 20% v/v ethanol or water for 2h or 4h (the last day) was overlaid during the time when the mice did not have nicotine available. Ethanol consumption (g/kg) and blood ethanol concentrations (BEC, mg %) were measured on the final day and whole brains including the cerebellum, were dissected for RNA sequencing. Differentially expressed genes (DEG) were detected with CuffDiff and gene networks were built using WGCNA. Prior nicotine exposure increased ethanol consumption and resulting BEC. Significant DEG and biological pathways found in the group exposed to both nicotine and ethanol included genes important in stress-related neuropeptide signaling, hypothalamic–pituitary–adrenal (HPA) axis activity, glutamate release, GABA signaling, and dopamine release. These results replicate our earlier findings that nicotine exposure during adolescence increases ethanol consumption and extends this work by examining gene expression differences which could mediate these behavioral effects.

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“…Ethanol-mediated effects on the transcriptome vary based on dose, method of administration, length of exposure, and brain region [ 62 ]. The method employed here was used to identify genes that were correlated to specific behaviors that were tested under identical treatment conditions [ 21 ] and would not necessarily be expected to be the same as those that change under other conditions of ethanol exposure, including in humans following many years of drinking.…”

Section: Discussionmentioning

confidence: 99%

Systems genetics analysis of the LXS recombinant inbred mouse strains:Genetic and molecular insights into acute ethanol tolerance

et al. 2020

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We have been using the Inbred Long- and Short-Sleep mouse strains (ILS, ISS) and a recombinant inbred panel derived from them, the LXS, to investigate the genetic underpinnings of acute ethanol tolerance which is considered to be a risk factor for alcohol use disorders (AUDs). Here, we have used RNA-seq to examine the transcriptome of whole brain in 40 of the LXS strains 8 hours after a saline or ethanol “pretreatment” as in previous behavioral studies. Approximately 1/3 of the 14,184 expressed genes were significantly heritable and many were unique to the pretreatment. Several thousand cis - and trans -eQTLs were mapped; a portion of these also were unique to pretreatment. Ethanol pretreatment caused differential expression (DE) of 1,230 genes. Gene Ontology (GO) enrichment analysis suggested involvement in numerous biological processes including astrocyte differentiation, histone acetylation, mRNA splicing, and neuron projection development. Genetic correlation analysis identified hundreds of genes that were correlated to the behaviors. GO analysis indicated that these genes are involved in gene expression, chromosome organization, and protein transport, among others. The expression profiles of the DE genes and genes correlated to AFT in the ethanol pretreatment group (AFT-Et) were found to be similar to profiles of HDAC inhibitors. Hdac1 , a cis -regulated gene that is located at the peak of a previously mapped QTL for AFT-Et, was correlated to 437 genes, most of which were also correlated to AFT-Et. GO analysis of these genes identified several enriched biological process terms including neuron-neuron synaptic transmission and potassium transport. In summary, the results suggest widespread genetic effects on gene expression, including effects that are pretreatment-specific. A number of candidate genes and biological functions were identified that could be mediating the behavioral responses. The most prominent of these was Hdac1 which may be regulating genes associated with glutamatergic signaling and potassium conductance.

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Transcriptional profiling of the rat nucleus accumbens after modest or high alcohol exposure

Cited by 7 publications

References 37 publications

Alcohol Activates Scabrous-Notch to Influence Associated Memories

Alcohol Activates Scabrous-Notch to Influence Associated Memories

The influence of adolescent nicotine exposure on ethanol intake and brain gene expression

Systems genetics analysis of the LXS recombinant inbred mouse strains:Genetic and molecular insights into acute ethanol tolerance

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