Drug Addiction and DNA Modifications

Brown, Amber N.; Feng, Jian

doi:10.1007/978-3-319-53889-1_6

Cited by 28 publications

(22 citation statements)

References 103 publications

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“…For more than a decade, the effects of drugs of abuse in the central nervous system have been shown to involve epigenetic changes on either histones or DNA . Concerning ethanol (EtOH), for example, a study showed in 2004 that chronic EtOH exposure increases expression of the GluN2B NMDA receptor subunit in cortical neurons through DNA demethylation .…”

Section: Introductionmentioning

confidence: 99%

Memory and plasticity impairment after binge drinking in adolescent rat hippocampus: GluN2A/GluN2B NMDA receptor subunits imbalance through HDAC2

et al. 2019

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Ethanol (EtOH) induces cognitive impairment through modulation of synaptic plasticity notably in the hippocampus. The cellular mechanism(s) of these EtOH effects may range from synaptic signaling modulation to alterations of the epigenome. Previously, we reported that two binge-like exposures to EtOH (3 g/kg, ip, 9 h apart) in adolescent rats abolished long-term synaptic depression (LTD) in hippocampus slices, induced learning deficits, and increased N-methyl-D-aspartate (NMDA) receptor signaling through its GluN2B subunit after 48 hours. Here, we tested the hypothesis of EtOH-induced epigenetic alterations leading to modulation of GluN2B and GluN2A NMDA receptor subunits. Forty-two days old rats were treated with EtOH or the histone deacetylase inhibitor (HDACi) sodium butyrate (NaB, 600 mg/kg, ip) injected alone or 30 minutes before EtOH. After 48 hours, learning was tested with novel object recognition while synaptic plasticity and the role of GluN2A and GluN2B subunits in NMDA-fEPSP were measured in CA1 field of hippocampus slices. LTD and memory were impaired 48 hours after EtOH and NMDA-fEPSP analysis unraveled changes in the GluN2A/GluN2B balance. These results were associated with an increase in histone deacetylase (HDAC) activity and HDAC2 mRNA and protein while Ac-H4K12 labelling was decreased. EtOH increases expression of HDAC2 and mRNA level for GluN2B subunit (but not GluN2A), while HDAC2 modulates the promoter of the gene encoding GluN2B. Interestingly, NaB pretreatment prevented all the cellular and memory-impairing effects of EtOH. In conclusion, the memoryimpairing effects of two binge-like EtOH exposure involve NMDA receptordependent LTD deficits due to a GluN2A/GluN2B imbalance resulting from changes in GluN2B expression induced by HDAC2. KEYWORDS epigenetic, ethanol, long-term depression Catherine Vilpoux and Olivier Pierrefiche are co-last authors. I.D., C.D., and R.A. performed and analyzed electrophysiology and behavior experiments; G.F., I.M., and V.D. performed and analyzed cellular biology; P.G., H.S., and C.V. performed and analyzed immunohistochemistry; S.P., M.N., C.V., and O.P. wrote and edited the manuscript. /journal/adb 1 of 15 2 | MATERIAL AND METHODS Experiments were performed following the European Community guiding principles for the care and use of animals (2010/63/UE, CE Off.

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Section: Introductionmentioning

confidence: 99%

Memory and plasticity impairment after binge drinking in adolescent rat hippocampus: GluN2A/GluN2B NMDA receptor subunits imbalance through HDAC2

et al. 2019

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“…Studies on rodents have proposed that prenatal alcohol exposure can give rise to epigenetic modifications ( Perkins et al 2013 ; Brown and Feng 2017 ; Chater-Diehl et al 2017 ; Tulisiak et al 2017 ). Future studies in Drosophila can assess whether prenatal alcohol exposure results in histone modifications that drive altered gene expression and, if so, to what extent such modifications persist across generations.…”

Section: Discussionmentioning

confidence: 99%

ACyclin ECentered Genetic Network Contributes to Alcohol-Induced Variation in Drosophila Development

Morozova

Hussain

McCoy

et al. 2018

G3 Genes|Genomes|Genetics

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Prenatal exposure to ethanol causes a wide range of adverse physiological, behavioral and cognitive consequences. However, identifying allelic variants and genetic networks associated with variation in susceptibility to prenatal alcohol exposure is challenging in human populations, since time and frequency of exposure and effective dose cannot be determined quantitatively and phenotypic manifestations are diverse. Here, we harnessed the power of natural variation in the Drosophila melanogaster Genetic Reference Panel (DGRP) to identify genes and genetic networks associated with variation in sensitivity to developmental alcohol exposure. We measured development time from egg to adult and viability of 201 DGRP lines reared on regular or ethanol- supplemented medium and identified polymorphisms associated with variation in susceptibility to developmental ethanol exposure. We also documented genotype-dependent variation in sensorimotor behavior after developmental exposure to ethanol using the startle response assay in a subset of 39 DGRP lines. Genes associated with development, including development of the nervous system, featured prominently among genes that harbored variants associated with differential sensitivity to developmental ethanol exposure. Many of them have human orthologs and mutational analyses and RNAi targeting functionally validated a high percentage of candidate genes. Analysis of genetic interaction networks identified Cyclin E (CycE) as a central, highly interconnected hub gene. Cyclin E encodes a protein kinase associated with cell cycle regulation and is prominently expressed in ovaries. Thus, exposure to ethanol during development of Drosophila melanogaster might serve as a genetic model for translational studies on fetal alcohol spectrum disorder.

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“…Instead it is likely that certain dietary factors alter endophenotypes that are relevant to a spectrum of mental illnesses. For instance, DNA methylation is affected in MDD, but also in drug addiction (Brown and Feng, 2017) and Alzheimer's disease (Qazi et al, 2018). Hence, altering the one-carbon metabolism through vitamins B9 and B12 may change the symptomology for all of these conditions.…”

Section: Conclusion -Nutrition An Depression: Researchers Still Have mentioning

confidence: 99%

The Way to a Human’s Brain Goes Through Their Stomach: Dietary Factors in Major Depressive Disorder

Aly

Engmann

2020

Front. Neurosci.

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Globally, more than 250 million people are affected by depression (major depressive disorder; MDD), a serious and debilitating mental disorder. Currently available treatment options can have substantial side effects and take weeks to be fully effective. Therefore, it is important to find safe alternatives, which act more rapidly and in a larger number of patients. While much research on MDD focuses on chronic stress as a main risk factor, we here make a point of exploring dietary factors as a somewhat overlooked, yet highly promising approach towards novel antidepressant pathways. Deficiencies in various groups of nutrients often occur in patients with mental disorders. These include vitamins, especially members of the B-complex (B6, B9, B12). Moreover, an imbalance of fatty acids, such as omega-3 and omega-6, or an insufficient supply with minerals, including magnesium and zinc, are related to MDD. While some of them are relevant for the synthesis of monoamines, others play a crucial role in inflammation, neuroprotection and the synthesis of growth factors. Evidence suggests that when deficiencies return to normal, changes in mood and behavior can be, at least in some cases, achieved. Furthermore, supplementation with dietary factors (so called “nutraceuticals”) may improve MDD symptoms even in the absence of a deficiency. Non-vital dietary factors may affect MDD symptoms as well. For instance, the most commonly consumed psychostimulant caffeine may improve behavioral and molecular markers of MDD. The molecular structure of most dietary factors is well known. Hence, dietary factors may provide important molecular tools to study and potentially help treat MDD symptoms. Within this review, we will discuss the role of dietary factors in MDD risk and symptomology, and critically discuss how they might serve as auxiliary treatments or preventative options for MDD.

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Drug Addiction and DNA Modifications

Cited by 28 publications

References 103 publications

Memory and plasticity impairment after binge drinking in adolescent rat hippocampus: GluN2A/GluN2B NMDA receptor subunits imbalance through HDAC2

Memory and plasticity impairment after binge drinking in adolescent rat hippocampus: GluN2A/GluN2B NMDA receptor subunits imbalance through HDAC2

ACyclin ECentered Genetic Network Contributes to Alcohol-Induced Variation in Drosophila Development

The Way to a Human’s Brain Goes Through Their Stomach: Dietary Factors in Major Depressive Disorder

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