Objective: Stress increases DNA methylation and decreases the expression of genes involved in neural plasticity, while treatment with DNA methyltransferase inhibitors (DNMTi) increases gene expression and induces antidepressant-like effects in preclinical models. Therefore, the aim of the present work was to further investigate the potential antidepressant-like effect induced by DNMTi by evaluating the behavioural effects induced by associating DNMTi treatment with conventional antidepressant drugs in mice submitted to the forced swimming test (FST). In addition, brain levels of DNA methylation were also investigated.
Methods: Mice received systemic injections of 5-aza-2'-deoxycytidine (5-AzaD, 0.1, 0.2 mg/kg), RG108 (0.1, 0.2, 0.4 mg/kg), desipramine (DES, 2.5, 5, 10 mg/kg) or fluoxetine (FLX, 5, 10, 20, 30 mg/kg) and were submitted to the FST or to the open field test (OFT). Additional groups received a combination of subeffective doses of 5-AzaD or RG108 (DNMTi) with subeffective doses of DES or FLX (antidepressants).
Results: Subeffective doses of RG108 (0.1 mg/kg) or 5-AzaD (0.1 mg/kg) in association with subeffective doses of DES (2.5 mg/kg) or FLX (10 mg/kg) induced significant antidepressant-like effects. Effective doses of RG108 (0.2 mg/kg), 5-AzaD (0.2 mg/kg), DES (10 mg/kg) and FLX (20 mg/kg) atenuated stress-induced changes in DNA methylation levels in the hippocampus and prefrontal cortex. None of the treatments induced locomotor effects in the OFT.
Conclusion: These results suggest that DNMTi potentiate the behavioural effects of antidepressant drugs in the FST and that antidepressants, as well as DNMTi, are able to modulate stress-induced changes in DNA methylation in brain regions closely associated with the neurobiology of depression.
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http://dx.doi.org/10.1017/neu.2015.40 | DOI Listing |
Cardiovasc Diabetol
January 2025
Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010, Málaga, Spain.
Background: The prevalence of obesity and type 2 diabetes mellitus (T2DM) is rising globally, particularly among children exposed to adverse intrauterine environments, such as those associated with gestational diabetes mellitus (GDM). Epigenetic modifications, specifically DNA methylation, have emerged as mechanisms by which early environmental exposures can predispose offspring to metabolic diseases. This study aimed to investigate DNA methylation differences in children born to mothers with GDM compared to non-GDM mothers, using saliva samples, and to assess the association of these epigenetic patterns with early growth measurements.
View Article and Find Full Text PDFNat Aging
January 2025
Program in Bioinformatics and Systems Biology, University of California, San Diego, La Jolla, CA, USA.
DNA methylation marks have recently been used to build models known as epigenetic clocks, which predict calendar age. As methylation of cytosine promotes C-to-T mutations, we hypothesized that the methylation changes observed with age should reflect the accrual of somatic mutations, and the two should yield analogous aging estimates. In an analysis of multimodal data from 9,331 human individuals, we found that CpG mutations indeed coincide with changes in methylation, not only at the mutated site but with pervasive remodeling of the methylome out to ±10 kilobases.
View Article and Find Full Text PDFJ Nutr
January 2025
Department of Animal Sciences, North Carolina State University, Raleigh, NC 27695, USA. Electronic address:
Background: Supplementing choline and docosahexaenoic acid (DHA) to pregnant gilts modified fetal pig hepatic global DNA methylation induced by gestational malnutrition, suggesting that gene expression and regulation and its associated metabolic pathways are affected in the liver of offspring during growth and development.
Objective: To investigate the effect of maternal supplementation of choline, DHA and their interaction on hepatic mRNA expression, miRNA regulation and metabolic pathways in the fetal pigs born to malnourished mothers.
Methods: The abundance of mRNA and miRNA was profiled in fetal liver from sows with undernutrition supplemented with choline and DHA in a 2 × 2 factorial design.
Microb Pathog
January 2025
Cell Biology and Molecular Genetics, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore 575018, INDIA. Electronic address:
Fungal hybrids arise through the interbreeding of distinct species. This hybridization process fosters increased genetic diversity and the emergence of new traits. Mechanisms driving hybridization include the loss of heterozygosity, copy number variations, and horizontal gene transfer.
View Article and Find Full Text PDFEnviron Toxicol Chem
January 2025
School of Environment and Energy, South China University of Technology, Guangzhou, PR China.
As a representative agent of bicyclic antidepressants, venlafaxine (VEN) has become widely used worldwide and is frequently detected in surface waters with concentrations ranging from ng/L to µg/L. To evaluate the toxicological effects of such medications on aquatic species, studies on environmentally relevant concentrations are essential. Zebrafish were used as a model organism to assess growth and development in larvae and examine tissue accumulation, oxidative stress, and DNA methylation in adults.
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