Chromatin Remodeling in Addiction: BRG1-SMAD3 Interaction Contributes to Cued Reinstatement of Cocaine Seeking

Smith, Alexander C.W.

doi:10.1016/j.biopsych.2016.09.003

Cited by 2 publications

(1 citation statement)

References 10 publications

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“…Notably, drug exposure (e.g., cocaine) induces SMAD3 interaction with BRG1 [ 29 ], an ATPase subunit of the SWI/SNF chromatin-remodeling complex, and negatively regulates cell proliferation and suppresses tumor pathogenesis. It has been reported that BRG1 incorporates into the transcriptional complexes of SMAD2/3-SMAD4 and modulates gene expression; however, the role of the SWI/SNF-BRG1-SMADs complex in gene regulation during drug addiction is unknown.…”

Section: Tgf-β/smad Signaling In Chromatin Regulation During Carcinog...mentioning

confidence: 99%

Oncogenic signaling-mediated regulation of chromatin during tumorigenesis

Alam

Huda

Tackett

et al. 2023

Cancer Metastasis Rev

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Signaling pathways play critical roles in executing and controlling important biological processes within cells. Cells/organisms trigger appropriate signal transduction pathways in order to turn on or off intracellular gene expression in response to environmental stimuli. An orchestrated regulation of different signaling pathways across different organs and tissues is the basis of many important biological functions. Presumably, any malfunctions or dysregulation of these signaling pathways contribute to the pathogenesis of disease, particularly cancer. In this review, we discuss how the dysregulation of signaling pathways (TGF-β signaling, Hippo signaling, Wnt signaling, Notch signaling, and PI3K-AKT signaling) modulates chromatin modifications to regulate the epigenome, thereby contributing to tumorigenesis and metastasis.

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Section: Tgf-β/smad Signaling In Chromatin Regulation During Carcinog...mentioning

confidence: 99%

Oncogenic signaling-mediated regulation of chromatin during tumorigenesis

Alam

Huda

Tackett

et al. 2023

Cancer Metastasis Rev

View full text Add to dashboard Cite

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Transcriptional characterization of cocaine withdrawal versus extinction within nucleus accumbens

Martínez-Rivera,

Holt,

Minier-Toribio

et al. 2024

Preprint

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Substance use disorder is characterized by a maladaptive imbalance wherein drug seeking persists despite negative consequences or drug unavailability. This imbalance correlates with neurobiological alterations some of which are amplified during forced abstinence, thereby compromising the capacity of extinction-based approaches to prevent relapse. Cocaine use disorder (CUD) exemplifies this phenomenon in which neurobiological modifications hijack brain reward regions such as the nucleus accumbens (NAc) to manifest craving and withdrawal-like symptoms. While increasing evidence links transcriptional changes in the NAc to specific phases of addiction, genome-wide changes in gene expression during withdrawal vs. extinction (WD/Ext) have not been examined in a context- and NAc-subregion-specific manner. Here, we used cocaine self-administration (SA) in rats combined with RNA-sequencing (RNA-seq) of NAc subregions (core and shell) to transcriptionally profile the impact of experiencing withdrawal in the home cage or in the previous drug context or experiencing extinction training. As expected, home-cage withdrawal maintained drug seeking in the previous drug context, whereas extinction training reduced it. By contrast, withdrawal involving repetitive exposure to the previous drug context increased drug-seeking behavior. Bioinformatic analyses of RNA-seq data revealed gene expression patterns, networks, motifs, and biological functions specific to these behavioral conditions and NAc subregions. Comparing transcriptomic analysis of the NAc of patients with CUD highlighted conserved gene signatures, especially with rats that were repetitively exposed to the previous drug context. Collectively, these behavioral and transcriptional correlates of several withdrawal-extinction settings reveal fundamental and translational information about potential molecular mechanisms to attenuate drug-associated memories.

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Chromatin Remodeling in Addiction: BRG1-SMAD3 Interaction Contributes to Cued Reinstatement of Cocaine Seeking

Cited by 2 publications

References 10 publications

Oncogenic signaling-mediated regulation of chromatin during tumorigenesis

Oncogenic signaling-mediated regulation of chromatin during tumorigenesis

Transcriptional characterization of cocaine withdrawal versus extinction within nucleus accumbens

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