ArticleClinical epigenetics2022
Psychostimulant-induced aberrant DNA methylation in an in vitro model of human peripheral blood mononuclear cells.
Article in Clinical epigenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 5 citations in OpenAlex.
- Influence of cocaine use reduction on markers of immune function.Journal of neuroimmunology · 2024Trial
- Epigenetic Regulation of Inflammation by Dopamine in Primary Human Macrophages.bioRxiv : the preprint server for biology · 2026Article
- Epigenetic regulation of inflammation by dopamine in primary human macrophages.Frontiers in immunology · 2026Article
- Concentration-dependent effect of delta-9-tetrahydrocannabinol on epigenetic DNA modifiers in human peripheral blood mononuclear cells.Translational psychiatry · 2025Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSeveral reports have provided crucial evidence in animal models that epigenetic modifications, such as DNA methylation, may be involved in psychostimulant-induced stable changes at the cellular level in the brain. Epigenetic editors DNA methyltransferases (DNMTs) and ten-eleven translocation enzymes (TETs) coordinate expression of gene networks, which then manifest as long-term behavioural changes. However, the extent to which aberrant DNA methylation is involved in the mechanisms of substance use disorder in humans is unclear. We previously demonstrated that cocaine modifies gene transcription, via DNA methylation, throughout the brain and in peripheral blood cells in mice.
resultsWe treated human peripheral blood mononuclear cells (PBMCs) from healthy male donors (n = 18) in vitro with psychostimulants (amphetamine, cocaine). After treatment, we assessed mRNA levels and enzymatic activities of TETs and DNMTs, conducted genome-wide DNA methylation assays and next-generation sequencing. We found that repeated exposure to psychostimulants decreased mRNA levels and enzymatic activity of TETs and 5-hydroxymethylation levels in PBMCs. These data were in line with observed hyper- and hypomethylation and mRNA expression of marker genes (IL-10, ATP2B4). Additionally, we evaluated whether the effects of cocaine on epigenetic editors (DNMTs and TETs) and cytokines interleukin-6 (IL-6) and IL-10 could be reversed by the DNMT inhibitor decitabine. Indeed, decitabine eliminated cocaine's effect on the activity of TETs and DNMTs and decreased cytokine levels, whereas cocaine increased IL-6 and decreased IL-10.
conclusionsOur data suggest that repeated psychostimulant exposure decreases TETs' enzymatic activity in PBMCs. Co-treatment with decitabine reversed TETs' levels and modulated immune response after repeated cocaine exposure. Further investigation is needed to clarify if TET could represent a putative biomarker of psychostimulant use and if DNMT inhibition could have therapeutic potential.
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