ArticleMolecular neurobiology2021
Modulation of DNA Methylation and Gene Expression in Rodent Cortical Neuroplasticity Pathways Exerts Rapid Antidepressant-Like Effects.
Article in Molecular neurobiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- Chronic unpredictable mild Stress- induced neurobehavioral and metabolic alteration: insights into molecular mechanisms and emerging therapeutic Strategies".Psychopharmacology · 2026Review
- Addictive drug abuse and depression-a focus on epigenetics.Communications biology · 2026Review
- Targeting Epigenetics in Ischemic Stroke: From Mechanisms to Therapeutics.Current neuropharmacology · 2026Review
- PRKCB methylation: a potential biomarker of MDD with childhood chronic stress, a cross-sectional study in drug-naive, first-episode adolescent MDD.Epigenetics · 2024Observational
- Article
- Curcumin can improve spinal cord injury by inhibiting DNA methylation.Molecular and cellular biochemistry · 2024Article
- L-methionine and the L-type CaFrontiers in neural circuits · 2024Article
- DNA methylation and the opposing NMDAR dysfunction in schizophrenia and major depression disorders: a converging model for the therapeutic effects of psychedelic compounds in the treatment of psychiatric illness.Molecular psychiatry · 2023Review
- Review
- The Cannabis-Induced Epigenetic Regulation of Genes Associated with Major Depressive Disorder.Genes · 2022Review
- Inhibition of DNA methylation during chronic obstructive bladder disease (COBD) improves function, pathology and expression.Scientific reports · 2021Article
- Decreased DNA methylation at promoters and gene-specific neuronal hypermethylation in the prefrontal cortex of patients with bipolar disorder.Molecular psychiatry · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundStress increases DNA methylation, primarily a suppressive epigenetic mechanism catalyzed by DNA methyltransferases (DNMT), and decreases the expression of genes involved in neuronal plasticity and mood regulation. Despite chronic antidepressant treatment decreases stress-induced DNA methylation, it is not known whether inhibition of DNMT would convey rapid antidepressant-like effects.
aimThis work tested such a hypothesis and evaluated whether a behavioral effect induced by DNMT inhibitors (DNMTi) corresponds with changes in DNA methylation and transcript levels in genes consistently associated with the neurobiology of depression and synaptic plasticity (BDNF, TrkB, 5-HT
methodsMale Wistar rats received intraperitoneal (i.p.) injection of two pharmacologically different DNMTi (5-AzaD 0.2 and 0.6 mg/kg or RG108 0.6 mg/kg) or vehicle (1 ml/kg), 1 h or 7 days before the learned helplessness test (LH). DNA methylation in target genes and the correspondent transcript levels were measured in the hippocampus (HPC) and prefrontal cortex (PFC) using meDIP-qPCR. In parallel separate groups, the antidepressant-like effect of 5-AzaD and RG108 was investigated in the forced swimming test (FST). The involvement of cortical BDNF-TrkB-mTOR pathways was assessed by intra-ventral medial PFC (vmPFC) injections of rapamycin (mTOR inhibitor), K252a (TrkB receptor antagonist), or vehicle (0.2 μl/side).
resultsWe found that both 5-AzaD and RG108 acutely and 7 days before the test decreased escape failures in the LH. LH stress increased DNA methylation and decreased transcript levels of BDNF IV and TrkB in the PFC, effects that were not significantly attenuated by RG108 treatment. The systemic administration of 5-AzaD (0.2 mg/kg) and RG108 (0.2 mg/kg) induced an antidepressant-like effect in FST, which was, however, attenuated by TrkB and mTOR inhibition into the vmPFC.
conclusionThese findings suggest that acute inhibition of stress-induced DNA methylation promotes rapid and sustained antidepressant effects associated with increased BDNF-TrkB-mTOR signaling in the PFC.
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