Oxidative DNA damage in the in utero initiation of postnatal neurodevelopmental deficits by normal fetal and ethanol-enhanced oxidative stress in oxoguanine glycosylase 1 knockout mice

Miller-Pinsler, Lutfiya; Pinto, Daniel; Wells, Peter G.

doi:10.1016/j.freeradbiomed.2014.09.026

Cited by 40 publications

(46 citation statements)

References 33 publications

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“…However, even physiological levels of ROS can be harmful in genetically or environmentally predisposed progeny, as they can cause altered signal transduction and/or oxidative macromolecular damage, including DNA damage and altered gene expression, which may contribute to teratogenesis (Figure ). For example, ROS‐initiated birth defects and postnatal neurodevelopmental abnormalities occur in untreated mutant or knockout (KO) mice with: (a) deficient ROS detoxification (glucose‐6‐phosphate dehydrogenase (G6PD; Nicol, Zielenski, Tsui, & Wells, ; Wells, Bhatia, Drake, & Miller‐Pinsler, ) or catalase (Abramov, Tran, Shapiro, & Wells, ; Abramov & Wells, ; Abramov & Wells, )); or (b) deficient DNA repair (oxoguanine glycosylase 1 (OGG1; Miller‐Pinsler et al, ; Miller‐Pinsler & Wells, ) or breast cancer 1 protein (BRCA1; Shapiro et al, )]. However, ROS levels in the fetus can also be enhanced by in utero exposure to environmental chemicals or drugs, resulting in oxidative stress.…”

Section: The Relationship Between Reactive Oxygen Species Oxidative mentioning

confidence: 99%

“…However, ROS levels in the fetus can also be enhanced by in utero exposure to environmental chemicals or drugs, resulting in oxidative stress. This has especially been implicated in the developmental toxicity of ethanol (EtOH; Dong, Sulik, & Chen, ; Miller, Shapiro, & Wells, ; Miller‐Pinsler et al, ; Miller‐Pinsler & Wells, ; Tables , Figure ) and several other drugs including methamphetamine (Cadet & Krasnova, ; Jeng, Wong, Ting‐A‐Kee, & Wells, ; Wong, McCallum, & Wells, ), phenytoin (Abramov et al, ; Abramov & Wells, ; Winn & Wells, ), and thalidomide (Hansen & Harris, ; Lee, Goncalves, & Wells, ; Parman, Wiley, & Wells, ; Knobloch, Schmitz, Götz, Schulze‐Osthoff, & Rüther, ), for which animal models reflect human developmental outcomes (Figures and ).…”

Section: The Relationship Between Reactive Oxygen Species Oxidative mentioning

confidence: 99%

“…Research suggests that 8‐oxoG is not only a mutagenic lesion causing cancer, but also leads to epigenetic modifications that alter and regulate gene expression (Bhatia & Wells, , ; Valinluck et al, ; Zarakowska, Gackowski, Foksinski, & Olinski, ). Since ROS may be a contributing mechanism in FASD (Brocardo et al, ; Miller‐Pinsler et al, ; Patten, Brocardo, Gil‐Mohapel, & Christie, ), EtOH‐enhanced 8‐oxoG levels may alter gene expression (without causing mutations) in genetically predisposed children such as those with a functional polymorphism in OGG1 that results in decreased DNA repair (Figures and ). In addition, environmental factors such as exposure to cadmium may also reduce OGG1 protein levels (Youn et al, ).…”

Section: Ros In Etoh‐initiated Birth Defects and Postnatal Neurodevelmentioning

confidence: 99%

“…However, the extent of ROS‐mediated direct alterations in developmental signal transduction pathways versus oxidative damage to embryonic and fetal cellular macromolecules like DNA is not known. Here, we discuss the evidence supporting the role of oxidative damage to macromolecules such as DNA, as a pathogenic mechanism involved in EtOH‐initiated embryopathies and neurodevelopmental abnormalities, which is evident at minimally developmentally toxic doses and concentrations of EtOH in various animal models via epigenetic and nonepigenetic mechanisms (Basavarajappa & Subbanna, ; Brooks, ; Galligan et al, ; Haycock, ; Mandal, Halder, Jung, & Chai, ; Miller‐Pinsler et al, ; Miller‐Pinsler & Wells, ; Shapiro et al, ; Shapiro, Miller, & Wells, , Ungerer et al, ; Varadinova & Boyadjieva, ; Tables , Figures & ). For example, a single administration of EtOH to gestational Day 17 pregnant dams increases the level of oxidatively damaged DNA (i.e., 8‐oxoG) in fetal brains of −/− Ogg1 mice lacking OGG1 (the major enzyme that repairs the 8‐oxoG lesion; Miller, Shapiro, Cheng, & Wells, ).…”

Section: Involvement Of Ros‐mediated Macromolecular Damage Versus Sigmentioning

confidence: 99%

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Oxidative stress and DNA damage in the mechanism of fetal alcohol spectrum disorders

Bhatia

Drake

Miller

et al. 2019

Birth Defects Research

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This review covers molecular mechanisms involving oxidative stress and DNA damage that may contribute to morphological and functional developmental disorders in animal models resulting from exposure to alcohol (ethanol, EtOH) in utero or in embryo culture. Components covered include: (a) a brief overview of EtOH metabolism and embryopathic mechanisms other than oxidative stress; (b) mechanisms within the embryo and fetal brain by which EtOH increases the formation of reactive oxygen species (ROS); (c) critical embryonic/fetal antioxidative enzymes and substrates that detoxify ROS; (d) mechanisms by which ROS can alter development, including ROS-mediated signal transduction and oxidative DNA damage, the latter of which leads to pathogenic genetic (mutations) and epigenetic changes; (e) pathways of DNA repair that mitigate the pathogenic effects of DNA damage; (f) related indirect mechanisms by which EtOH enhances risk, for example by enhancing the degradation of some DNA repair proteins; and, (g) embryonic/fetal pathways like NRF2 that regulate the levels of many of the above components. Particular attention is paid to studies in which chemical and/or genetic manipulation of the above mechanisms has been shown to alter the ability of EtOH to adversely affect development. Alterations in the above components are also discussed in terms of: (a) individual embryonic and fetal determinants of risk and (b) potential risk biomarkers and mitigating strategies. FASD risk is likely increased in progeny which/who are biochemically predisposed via genetic and/or environmental mechanisms, including enhanced pathways for ROS formation and/or deficient pathways for ROS detoxification or DNA repair.

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Section: The Relationship Between Reactive Oxygen Species Oxidative mentioning

confidence: 99%

Section: The Relationship Between Reactive Oxygen Species Oxidative mentioning

confidence: 99%

Section: Ros In Etoh‐initiated Birth Defects and Postnatal Neurodevelmentioning

confidence: 99%

Section: Involvement Of Ros‐mediated Macromolecular Damage Versus Sigmentioning

confidence: 99%

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Oxidative stress and DNA damage in the mechanism of fetal alcohol spectrum disorders

Bhatia

Drake

Miller

et al. 2019

Birth Defects Research

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“…The other is oxoguanine glycosylase 1 (OGG1), a DNA repair enzyme and biomarker of oxidative stress. Mice homozygous for a null OGG1 mutation are more impaired than wild type by alcohol on a passive avoidance test and have increased oxidatively damaged DNA (Miller-Pinsler et al, 2015). …”

Section: Discussionmentioning

confidence: 99%

Importance of genetics in fetal alcohol effects: Null mutation of the nNOS gene worsens alcohol-induced cerebellar neuronal losses and behavioral deficits

et al. 2015

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The cerebellum is a major target of alcohol-induced damage in the developing brain. However, the cerebella of some children are much more seriously affected than others by prenatal alcohol exposure. As a consequence of in utero alcohol exposure, some children have substantial reductions in cerebellar volume and corresponding neurodevelopmental problems, including microencephaly, ataxia, and balance deficits, while other children who were exposed to similar alcohol quantities are spared. One factor that likely plays a key role in determining the impact of alcohol on the fetal cerebellum is genetics. However, no specific gene variant has yet been identified that worsens cerebellar function as a consequence of developmental alcohol exposure. Previous studies have revealed that mice carrying a homozygous mutation of the gene for neuronal nitric oxide synthase (nNOS−/− mice) have more severe acute alcohol-induced neuronal losses from the cerebellum than wild type mice. Therefore, the goals of this study were to determine whether alcohol induces more severe cerebellum-based behavioral deficits in nNOS−/− mice than in wild type mice and to determine whether these worsened behavior deficits are associated with worsened cerebellar neuronal losses. nNOS−/− mice and their wild type controls received alcohol (0.0, 2.2, or 4.4 mg/g) daily over postnatal days 4–9. In adulthood, the mice underwent behavioral testing, followed by neuronal quantification. Alcohol caused dose-related deficits in rotarod and balance beam performance in both nNOS−/− and wild type mice. However, the alcohol-induced behavioral deficits were substantially worse in the nNOS−/− mice than in wild type. Likewise, alcohol exposure led to losses of Purkinje cells and cerebellar granule cells in mice of both genotypes, but the cell losses were more severe in the nNOS−/− mice than in wild type. Behavioral performances were correlated with neuronal number in the nNOS−/− mice, but not in wild type. Thus, homozygous mutation of the nNOS gene increases vulnerability to alcohol-induced cerebellar dysfunction and neuronal loss. nNOS is the first gene identified whose mutation worsens alcohol-induced cerebellar behavioral deficits.

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Mechanisms involved in the neurotoxic and cognitive effects of developmental methamphetamine exposure

Jablonski

Williams

2016

Birth Defects Research Pt C

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Methamphetamine exposure in utero leads to a variety of higher-order cognitive deficits, such as decreased attention and working, and spatial memory impairments in exposed children (Piper et al., 2011; Roussotte et al., 2011; Kiblawi et al., 2011). As with other teratogens, the timing of methamphetamine exposure greatly determines its effects on both neuroanatomical and behavioral outcomes. Methamphetamine exposure in rodents during the third trimester human equivalent period of brain development results in distinct and long-lasting route-based and spatial navigation deficits (Williams et al., 2003; Vorhees et al., 2005, 2008, 2009;). Here, we examine the impact of neonatal methamphetamine-induced neurotoxicity on behavioral outcomes, neurotransmission, receptor changes, plasticity proteins, and DNA damage. Birth Defects Research (Part C) 108:131-141, 2016. © 2016 Wiley Periodicals, Inc.

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Oxidative DNA damage in the in utero initiation of postnatal neurodevelopmental deficits by normal fetal and ethanol-enhanced oxidative stress in oxoguanine glycosylase 1 knockout mice

Cited by 40 publications

References 33 publications

Oxidative stress and DNA damage in the mechanism of fetal alcohol spectrum disorders

Oxidative stress and DNA damage in the mechanism of fetal alcohol spectrum disorders

Importance of genetics in fetal alcohol effects: Null mutation of the nNOS gene worsens alcohol-induced cerebellar neuronal losses and behavioral deficits

Mechanisms involved in the neurotoxic and cognitive effects of developmental methamphetamine exposure

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