Erratum: Increased OPRM1 DNA Methylation in Lymphocytes of Methadone

Nielsen, David A.; Yuferov, Vadim; Hamon, Sara; Jackson, Colin; Ho, Ann; Ott, Jürg; Kreek, Mary Jeanne

doi:10.1038/npp.2008.155

Cited by 3 publications

(7 citation statements)

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“…As reported previously (Nielsen et al, 2009, 2010), possible methylation patterns and bisulfite-altered nucleotides were designed using the Methyl Primer Express 1.0 software (ABI). Predicted bisulfite-treated and untreated sequences were exported to Vector NTI Advance 11 (Invitrogen, Carlsbad, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Percent cytosine methylation was determined as previously described (Nielsen et al, 2009). Briefly, genomic DNA (300 ng) was treated with sodium bisulfite using the EZ-96 DNA Methylation Kit D5004 (Zymo Research, Orange, CA, USA) and amplified (Nielsen et al, 2009).…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, genomic DNA (300 ng) was treated with sodium bisulfite using the EZ-96 DNA Methylation Kit D5004 (Zymo Research, Orange, CA, USA) and amplified (Nielsen et al, 2009). DNA was amplified with the primer sets listed in Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…There is evidence that the production of these proteins is affected by chromatin associated changes since an age related decline of histone deacetylation and methylation in the chromatin of oligodenrocytes in the corpus callosum has been observed, an effect that could at least partially explain the age related reduction in the ability of the brain to repair myelin (Shen et al, 2008). Other drugs of abuse have been shown to have chromatin associated effects; repeated treatment with opioids has been shown to be associated with alterations of DNA methylation (Nielsen et al, 2009, 2010). However, no study to date has examined epigenetic mechanisms associated with myelin production during withdrawal from self-administered cocaine.…”

Section: Introductionmentioning

confidence: 99%

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Forced Abstinence from Cocaine Self-Administration is Associated with DNA Methylation Changes in Myelin Genes in the Corpus Callosum: a Preliminary Study

Nielsen¹,

Huang²,

Hamon³

et al. 2012

Front. Psychiatry

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Background: Human cocaine abuse is associated with alterations in white matter integrity revealed upon brain imaging, an observation that is recapitulated in an animal model of continuous cocaine exposure. The mechanism through which cocaine may affect white matter is unknown and the present study tested the hypothesis that cocaine self-administration results in changes in DNA methylation that could result in altered expression of several myelin genes that could contribute to the effects of cocaine on white matter integrity. Methods: In the present study, we examined the impact of forced abstinence from cocaine self-administration on chromatin associated changes in white matter. To this end, rats were trained to self-administer cocaine (0.75 mg/kg/0.1 mL infusion) for 14 days followed by forced abstinence for 1 day (n = 6) or 30 days (n = 6) before sacrifice. Drug-free, sham surgery controls (n = 7) were paired with the experimental groups. Global DNA methylation and DNA methylation at specific CpG sites in the promoter regions ofmyelin basic protein (Mbp), proteolipid protein-1 (Plp1), and SRY-related HMG-box-10 (Sox10) genes were analyzed in DNA extracted from corpus callosum. Results: Significant differences in the overall methylation patterns of the Sox10 promoter region were observed in the corpus callosum of rats at 30 days of forced abstinence from cocaine self-administration relative to sham controls; the −189, −142, −93, and −62 CpG sites were significantly hypomethylated point-wise at this time point. After correction for multiple comparisons, no differences in global methylation or the methylation patterns of Mbp or Plp1 were found. Conclusion: Forced abstinence from cocaine self-administration was associated with differences in DNA methylation at specific CpG sites in the promoter region of the Sox10 gene in corpus callosum. These changes may be related to reductions in normal age related changes in DNA methylation and could be a factor in white matter alterations seen after withdrawal from repeated cocaine self-administration. Further research is warranted examining the effects of cocaine on DNA methylation in white matter.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Forced Abstinence from Cocaine Self-Administration is Associated with DNA Methylation Changes in Myelin Genes in the Corpus Callosum: a Preliminary Study

Nielsen¹,

Huang²,

Hamon³

et al. 2012

Front. Psychiatry

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“…Studies have shown that individual genetic variants are associated with risk of substance abuse, including CD [but usually only in select populations, e.g., OPRM1 (Berrettini et al, 1997), Homer1 (Dahl et al, 2005), OPRD1 (Kreek et al, 2005; Crist et al, 2012)] but also that epigenetics may play a significant role in the disease process (e.g., Nielsen et al, 2009, 2010). Changes in epigenetics, including chromatin structure and DNA methylation, due to drug use, and the resulting change in gene expression are hypothesized to contribute to the neural plasticity in drug users that has long been considered a molecular mechanism through which drug addiction and relapse may occur (e.g., Berke et al, 1998; Nestler, 2001; Grimm et al, 2003; Yao et al, 2004; Shaham and Hope, 2005; Kalivas and O’Brien, 2008; Wong et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

The MTHFR C677T Variant is Associated with Responsiveness to Disulfiram Treatment for Cocaine Dependency

et al. 2013

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Objective: Disulfiram is a one of the few pharmacotherapies for cocaine addiction that shows promise. Since disulfiram and cocaine both affect levels of global methylation we hypothesized the MTHFR gene, whose product is involved in supplying methyl groups for DNA and protein methylation, may be associated with responsiveness to disulfiram in cocaine-dependent individuals. Methods: Sixty-seven cocaine-dependent patients were stabilized on methadone for 2 weeks and then randomized into disulfiram (250 mg/day, N = 32) and placebo groups (N = 35) for 10 weeks. Patients were genotyped for the MTHFR (rs1801133, also known as C677T) polymorphism and the data was evaluated for association with cocaine-free urines in the disulfiram or placebo groups. Data from patients that completed all 10 weeks of the study (N = 56) were analyzed using repeated measures analysis of variance (ANOVA), corrected for population structure. Results: The CT or TT MTHFR genotype group (N = 32) dropped from 73 to 52% cocaine-positive urines on disulfiram (p = 0.0001), while the placebo group showed no treatment effect. The CC MTHFR genotype group (N = 24) showed a smaller, but still significant, reduction in cocaine-positive urines on disulfiram compared to placebo; 81–69% (p = 0.007). Conclusion: This study indicates that a patient’s MTHFR genotype may be used to identify individuals who might show improved response to disulfiram treatment for cocaine dependence. Clinical Trial: Pharmacogenetics of Disulfiram for Cocaine, clinicaltrials.gov/ct2/show/NCT00149630, NIDA-18197-2, NCT00149630.

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The role of the gut microbiome and microbial metabolism in mediating opioid-induced changes in the epigenome

Kolli,

Roy

2023

Front. Microbiol.

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The current opioid pandemic is a major public health crisis in the United States, affecting millions of people and imposing significant health and socioeconomic burdens. Preclinical and clinical research over the past few decades has delineated certain molecular mechanisms and identified various genetic, epigenetic, and environmental factors responsible for the pathophysiology and comorbidities associated with opioid use. Opioid use-induced epigenetic modifications have been identified as one of the important factors that mediate genetic changes in brain regions that control reward and drug-seeking behavior and are also implicated in the development of tolerance. Recently, it has been shown that opioid use results in microbial dysbiosis, leading to gut barrier disruption, which drives systemic inflammation, impacting the perception of pain, the development of analgesic tolerance, and behavioral outcomes. In this review, we highlight the potential role of microbiota and microbial metabolites in mediating the epigenetic modifications induced by opioid use.

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Erratum: Increased OPRM1 DNA Methylation in Lymphocytes of Methadone

Cited by 3 publications

References 0 publications

Forced Abstinence from Cocaine Self-Administration is Associated with DNA Methylation Changes in Myelin Genes in the Corpus Callosum: a Preliminary Study

Forced Abstinence from Cocaine Self-Administration is Associated with DNA Methylation Changes in Myelin Genes in the Corpus Callosum: a Preliminary Study

The MTHFR C677T Variant is Associated with Responsiveness to Disulfiram Treatment for Cocaine Dependency

The role of the gut microbiome and microbial metabolism in mediating opioid-induced changes in the epigenome

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