Characterization of Oral-to-Blood Microbial DNA Translocation in Chronic Cocaine Use Disorder
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE304577 | GEO | 2026/02/24
REPOSITORIES: GEO
Similar Datasets
Project description:Cocaine use disorder (CUD) is a chronic neuropsychiatric condition characterized by a compulsion to use cocaine, resulting from enduring cellular and molecular adaptations. Among substance use disorders (SUDs), CUD is notable for its rising prevalence and the lack of approved pharmacotherapies. The nucleus accumbens (NAc), integral to the brain's reward circuitry, plays a crucial role in the initiation and continuation of maladaptive behaviors intrinsic to CUD. Leveraging advancements in neuroproteomics, we undertook an in-depth proteomic analysis of the NAc in a mouse model that spans membrane, cytosolic, nuclear, and chromatin compartments. Our study unveils immediate and sustained proteomic modifications post-cocaine exposure and during prolonged withdrawal. We identify congruent protein regulatory patterns during initial cocaine exposure and re-exposure post-withdrawal, contrasted against distinct patterns during withdrawal. Pronounced proteomic shifts within the membrane compartment indicate adaptive and long-lasting molecular responses prompted by cocaine withdrawal. Additionally, we describe protein translocation events between soluble-nuclear and chromatin-bound compartments, providing novel insight into intracellular protein dynamics post-cocaine exposure. Together, our findings illuminate the intricate proteomic landscape altered in the NAc by cocaine and provide a comprehensive dataset for future research toward potential therapeutics.
2025-05-06 | PXD050162 | Pride
Project description:Characterization of Oral-to-Blood Microbial DNA Translocation in Chronic Cocaine Use Disorder
| PRJNA1301822 | ENA
Project description:We cataloged miRNA expression in the nucleus accumbens and at striatal synapses in control and chronically cocaine-treated mice. We identified cocaine-responsive miRNAs, synaptically-enriched and depleted miRNA families, and confirmed cocaine-induced changes in protein expression for several predicted synaptic target genes. Analysis of small RNA from Mus musculus nucleus accumbens (NAc) and postsynaptic densities (PSD) with and without chronic cocaine treatment.
2011-05-13 | E-GEOD-29261 | biostudies-arrayexpress
Project description:Cocaine is one of the most abused psychostimulants in the United States. In addition to its established roles in the regulation of dopaminergic circuitries, cocaine has a broader mechanism of action, including global alterations in brain metabolism and mitochondrial homeostasis. Our group recently identified a subpopulation of non-microvesicular, non-exosomal extracellular vesicles of mitochondrial origin, mitovesicles (mtVs), and provided a method to isolate mtVs from brain parenchyma. Given their origin, we hypothesized that mtVs could be affected by mitochondrial abnormalities induced by chronic cocaine exposure. Therefore, we analyzed mtVs from hemibrains of 3-month-old mice that received for two weeks intraperitoneal injections of cocaine or saline as control. MtVs from the brain extracellular space of cocaine-intoxicated mice were enlarged and more numerous when compared to controls. Moreover, cocaine stimulated higher intracellular mitochondrial fission and higher levels of upstream (but not downstream) mitophagy pathways, suggesting increased mitochondrial fragmentation and a block in mitophagy flux. Lastly, cocaine impaired brain mtV cargo loading as revealed by Mass Spec analysis, causing an alteration in mtV ATP production capacity. These data suggest that mtVs are a previously unidentified player in the biology of cocaine addiction and that target therapies to fine tune brain mtV functionality may be beneficial to mitigate chronic cocaine pathology.
2022-04-27 | MSV000089323 | MassIVE
Project description:Substance use disorder emerges in a small proportion of drug users and has the characteristics of a chronic relapsing pathology. The objective of our study was to demonstrate and characterize the variability in the expression of the reinforcing effects of cocaine in the conditioned place preference (CPP) paradigm. An unbiased cocaine-CPP paradigm in Sprague-Dawley rats with an extinction period of 12 days and reinstatement was conducted. We developed a statistical model to distinguish rats that express or do not express cocaine-induced place preference. Two groups of rats were identified: rats that did express reinforcing effects (CPP expression (CPPE), score > 102 s) and rats that did not (no CPP expression (nCPPE), score between −85 and 59 s). These two groups did not show significant differences in a battery of behavioral tests. To identify differentially expressed genes in the CPPE and nCPPE groups, we performed a whole-transcriptome RNA-sequencing analysis in the nucleus accumbens (Nac) 24 h after the CPP test. Four immediate early genes (Fos, Egr2, Nr4a1 and Zbtb37) were differentially expressed in the Nac of CPPE rats after CPP memory retrieval. Variability in cocaine-induced place preference persisted in the CPPE and nCPPE groups after the extinction and reinstatement phases. Transcriptomic differences observed after reinstatement were distinct from those observed immediately after CPP memory retrieval. These new findings provide insights into the identification of mechanisms underlying interindividual variability in the response to cocaine's reinforcing effects.
2024-03-11 | GSE169666 | GEO
Project description:In this paper, we first report that EC smoking significantly increases the odds of gingival inflammation. Then, we seek to identify and explain the mechanism that underlies the relationship between EC smoking and gingival inflammation via the oral microbiome. We performed mediation analyses to assess if EC smoking affects the oral microbiome, which in turn affects gingival inflammation. For this, we collected saliva and subgingival samples from EC users and non-users and profiled their microbial compositions via 16S rRNA amplicon sequencing. We then performed α-diversity, β-diversity, and taxonomic differential analyses to survey the disparity in microbial composition between EC users and non-users. We found significant increases in α-diversity in EC users and disparities in β-diversity between EC users and non-users.
2022-12-09 | GSE201949 | GEO
Project description:Substance use disorder (SUD) is a chronic neuropsychiatric condition characterized by long-lasting alterations in the neural circuitry regulating reward and motivation. Substantial work has focused on characterizing the molecular substrates which underlie these persistent changes in neural function and behavior; however, this work has overwhelmingly focused on male subjects, despite mounting clinical and preclinical evidence that females demonstrate dissimilar progression to SUD and responsivity to drugs of abuse, such as cocaine. Here, we show that sex is a critical biological variable that defines drug-induced plasticity in the NAc. Using quantitative mass spectrometry, we assessed the protein expression patterns altered by cocaine self-administration and demonstrate unique molecular profiles between males and females. We show that 1. Cocaine self-administration induces non-overlapping protein expression patterns in males and females and 2. Cocaine specifically acts on baseline sexual dimorphisms to exert these effects. Critically, we find that cocaine administration blunts not only basal sex-differences in the accumbens proteome, but also the pre-existing sex differences in behavior for natural rewards. Together, these data suggest that chronic cocaine is capable of rewriting baseline proteomic function to maintain cocaine-specific behaviors.
2021-09-09 | PXD022832 | Pride
Project description:Cocaine-induced alterations in gene expression cause changes in neuronal morphology and behavior that may underlie cocaine addiction. We identified an essential role for histone 3 lysine 9 (H3K9) dimethylation and the lysine dimethyltransferase G9a in cocaine-induced structural and behavioral plasticity. Repeated cocaine administration reduced global levels of H3K9 dimethylation in the nucleus accumbens. This reduction in histone methylation was mediated through the repression of G9a in this brain region. To identify whether changes in H3K9me2 correlated with genome-wide alterations in gene expression in the NAc, we employed microarray analyses to examine gene expression profiles induced by a challenge dose of cocaine in animals with or without a history of prior cocaine exposure. Animals that had received repeated cocaine displayed dramatically increased gene expression 1 hour after a cocaine challenge in comparison to acutely treated animals. This increased gene expression still occurred in response to a cocaine challenge given after 1 week of withdrawal from repeated cocaine. These data suggest that repeated, but not acute, cocaine exposure results in persistent sensitized genomic responses to a cocaine challenge, indicating that sensitized behavioral responses to repeated cocaine are likely the result of G9a-dependent alterations in global transcriptional responses to cocaine.
2009-10-28 | GSE18751 | GEO
Project description:Ventral hippocampus (vHPC) CA1 pyramidal neurons send glutamatergic projections to nucleus accumbens (NAc), and this vHPC-NAc circuit mediates cocaine seeking and reward, but it is unclear whether vHPC-NAc neuron properties are modulated by cocaine exposure to drive subsequent behavior. The immediate early gene transcription factor ΔFosB is induced throughout the brain by cocaine and is critical for cocaine seeking, but it’s function in vHPC-NAc neurons is not understood. We now show that circuit-specific knockout of ΔFosB in vHPC-NAc neurons impaired cocaine reward expression and forced abstinence-induced seeking. We also found that vHPC-NAc excitability was decreased by experimenter-administered repeated cocaine and cocaine self-administration, and this cocaine-induced excitability decrease was mediated by ΔFosB expression. To uncover the mechanism of this change in circuit function, we used circuit-specific translating ribosome affinity purification (TRAP) to assess cocaine-induced, ΔFosB-dependent changes in gene expression in vHPC-NAc. We found that cocaine causes a ΔFosB-dependent increase in the expression of calreticulin, an ER-resident calcium-buffering protein. Calreticulin expression mediated vHPC-NAc excitability and was necessary for cocaine reward. These findings uncover a novel, non-canonical mechanism by which cocaine increases calreticulin in vHPC leading to decreased vHPC-NAc excitability and drive cocaine seeking and reward.
2026-01-10 | GSE281142 | GEO
Project description:Cocaine use disorder (CUD) is an intractable syndrome, and rising overdose death rates represent a significant public health crisis that exacts tremendous personal and financial costs on patients and society. Sharp increases in cocaine use drive the urgent need for better mechanistic insight into this chronic relapsing brain disorder that currently lacks effective treatment options. To investigate the transcriptomic changes involved, we conducted RNA sequencing on two striatal brain regions that are heavily implicated in CUD, the nucleus accumbens and caudate nucleus, from postmortem brains of subjects with CUD and matched control subjects. Weighted gene co-expression analyses identified CUD-specific gene networks enriched in ionotropic receptors and associated with lowered neuroinflammation, contrasting the proinflammatory responses found in opioid use disorder. Integration of comprehensive transcriptomic datasets from mouse cocaine self-administration models revealed evolutionarily conserved gene networks in CUD that implicate especially D1 medium spiny neurons as drivers of cocaine-induced plasticity.
2022-12-19 | GSE214267 | GEO