Changes in the Expression of DNA Methylation Related Genes in Leukocytes of Persons with Alcohol and Drug Dependence

Krasteva, Maria; Koycheva, Yana; Taseva, Teodora; Simeonova, Stiliana

doi:10.2478/amb-2020-0039

Cited by 3 publications

(4 citation statements)

References 43 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While MeCP2 does not directly measure DNA methylation, its key role in the methylation process suggests alterations in global methylation patterns in the liver due to ethanol. This lines up with other areas also showing altered MeCP2 expression after ethanol exposure and changes to this regulation after treatment for AUD (Aşçibaşi et al, 2023;Cui et al, 2020;Krasteva et al, 2020). The changes in Mecp2 expression raise questions about the longterm alterations of global methylation patterns and how these might play a role in inheritance.…”

Section: Methylation Changes and Intergenerational Inheritancesupporting

confidence: 64%

“…Studies which examine specific genes in individuals have seen an increase in DNA methylation and a reduction in gene expression of Period Circadian Regulator 2 (PER2) and Proopiomelanocortin (POMC) in heavy drinkers which were predictors of alcohol craving (Gangisetty et al, 2019;Muschler et al, 2010). Assessment of DNMTs show lowered DNMT-3b mRNA expression is associated with an increase of genomic DNA methylation in patients with alcoholism (Bönsch et al, 2006) and another study of DNMTs and methyl-CpG-binding domain proteins in the blood of individuals with AUD also show a downregulation of methyl-CpG binding domain protein 1 (MBD1) and methyl-CpG-binding protein 2 (MECP2/Mecp2) in the alcohol-dependent group (Krasteva et al, 2020). Interestingly, these differences in methylation seem to be related to patterns of consumptions with one study finding significantly lower DNA methylation levels in the leukocytes of heavy drinkers compared to non-drinkers and moderate drinkers when looked at cross-sectionally (Maeda et al, 2022) and another reported differential blood DNA methylation in certain CpG islands in former drinkers compared to current drinkers in a longitudinal study (Dugué et al, 2021).…”

Section: Human Studiesmentioning

confidence: 97%

“…This study, along with others, has shown that alcohol causes changes in those directly exposed to it. Some of these include changes in epigenetic modifications in the liver, blood, and brain regions as well as alterations in reward, HPA and cognitive pathways (Ajoolabady et al, 2023;Gangisetty et al, 2019;Krasteva et al, 2020). While the mechanisms are still unclear, the behavioural phenotypes reported in the F1 and F2 generations indicate these changes are more likely to be passed down to the offspring through epigenetic changes rather than genetic mutations.…”

Section: Mechanisms Of Ppacmentioning

confidence: 99%

See 2 more Smart Citations

Transgenerational Hangovers: A Rat Model for Behavioural and Epigenetic Changes Across Generations due to Paternal Preconceptual Alcohol Consumption

Hussain

View full text Add to dashboard Cite

Alcohol is the most harmful drug of abuse, making alcoholism a major economic and public health crisis. Unsurprisingly, this has led to the majority of neurobiological research on alcohol focussing on its direct effects on an individual. This includes those affected by foetal alcohol spectrum disorders (FASDs). However, research has shown that heavy paternal drinking predicts earlier and heavier adolescent drinking in the offspring, accompanied with other behavioural and molecular changes. While alcohol use disorder (AUD) is highly heritable, research on genetic variants alone does not sufficiently account for its risk and the FASDs like symptoms seen in the offspring of alcoholic fathers. Recently, there has been an increase in appreciation of the importance of epigenetic mechanisms of inheritance, which transfer changes due to parental experiences through the germline. This thesis aimed to assess both the inter and transgenerational impacts of preconceptual paternal alcohol consumption (PPAC) using a rat model. Sprague Dawley male rats (F0) underwent chronic voluntary ethanol intake and at the end of the drinking paradigm were kept for one spermatogenesis cycle before being mated with ethanol naïve females. The litters and matched controls were behaviourally assessed, and a cohort of F1 males mated to observe a F2 generation.PPAC caused behavioural changes in both the F1 and F2 generations, including altering litter sizes and delaying development. The F1 also show a reduction in sensitivity to the motor impairing effects of ethanol compared to controls. Sexually dimorphic effects of PPAC were seen with female offspring having a reduced preference to ethanol in both the F1 and F2, while tolerance to ethanol in motor coordination was again seen in the F2 females but not F2 males. Likewise, F1 males presented reductions in locomotor activity but these effects did not persist in the F2.Analysis of liver mitochondrial DNA copy number (mtDNA-CN) found that drinking F0 fathers had reduced mtDNA-CN at the end of the ethanol intake paradigm and 12 weeks post-drinking relative to controls. The livers of F1 showed lower mtDNA-CN in the offspring of ethanol sired rats compared to offspring of non-drinkers after undergoing ethanol consumption, suggesting differences in liver metabolism. Finally, livers of F0 drinkers had reduced expression of Peroxisome proliferator-activated receptor γ coactivator 1α (Pgc1a), relating to mitochondrial biogenesis, and methyl-CpG-binding protein 2 (Mecp2), indicating putative changes in methylation signalling, together suggesting epigenetic inheritance of changes due to xenotoxic stress.The findings show PPAC induces developmental delays, causes transgenerational changes in drinking behaviour, ethanol sensitivity and liver mitochondrial function in a sexually dimorphic manner. These changes may be protective to the female offspring of PPAC to modify their ethanol intake. The alterations in F1 liver mtDNA-CN demonstrate potential far-reaching consequences for the metabolism of xenotoxic substances extending beyond ethanol and provides evidence to support behavioural and epigenetic changes across generations due to PPAC.

show abstract

Section: Methylation Changes and Intergenerational Inheritancesupporting

confidence: 64%

Section: Human Studiesmentioning

confidence: 97%

Section: Mechanisms Of Ppacmentioning

confidence: 99%

See 1 more Smart Citation

Transgenerational Hangovers: A Rat Model for Behavioural and Epigenetic Changes Across Generations due to Paternal Preconceptual Alcohol Consumption

Hussain

View full text Add to dashboard Cite

show abstract

“…These higher levels of DNA methylation were predictors of increased subjective alcohol craving and were associated with the amount of alcohol consumed during the Alcohol Taste Test [23,33]. Krasteva et al (2020) evaluated DNMT1, DNMT3a, and methyl-CpG-binding domain proteins in the blood of individuals with AUD, finding downregulation of MeCP2 and MBD1 in the alcohol-dependent group [34].…”

Section: Human Studiesmentioning

confidence: 99%

Alcohol: Epigenome Alteration and Transgenerational Effect

Heidari¹,

Hajikarim-Hamedani²,

Heidari³

et al. 2023

Preprint

View full text Add to dashboard Cite

While DNA serves as the fundamental genetic blueprint for an organism, it is not a static entity. Gene expression, the process by which genetic information is utilized to create functional products like proteins, can be modulated by a diverse range of environmental factors. Epigenetic mechanisms, encompassing DNA methylation, histone modification, and microRNAs, play a pivotal role in mediating the intricate interplay between the environment and gene expression. Intriguingly, alterations in the epigenome have the potential to be inherited across generations. Ethanol abuse poses significant health issues worldwide. Ethanol has the capability to induce changes in the epigenome, which can be inherited by offspring, thus impacting them even in the absence of direct ethanol exposure. This review article reviewed the alterations caused by ethanol on the epigenome. We thoroughly gathered all relevant papers investigating the behavioral and molecular consequences of parental ethanol exposure on their offspring. In conclusion, the comprehensive analysis of the literature supports the notion that ethanol exposure induces lasting epigenetic alterations, which can influence the behavior and health of future generations. This knowledge emphasizes the significance of addressing the potential transgenerational effects of ethanol and highlights the importance of preventive measures to minimize the adverse impact on offspring.

show abstract