scholarly journals Mechanisms of Prenatal Ethanol Exposure on Causing Developmental Defects Associated with Fetal Alcohol Syndrome Disorders

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Jordan Powerll
1995 ◽  
Vol 73 (9) ◽  
pp. 1209-1223 ◽  
Author(s):  
James D. Reynolds ◽  
James F. Brien

The purpose of this article is to review the current state of knowledge of ethanol neurobehavioural teratogenesis and its postulated mechanisms. The review comprises an examination of ethanol teratogenesis in the human, including the fetal alcohol syndrome, and in experimental animals. Several current proposed mechanisms of ethanol neurobehavioural teratogenesis are critically assessed, including the role of acetaldehyde as the proximate metabolite of ethanol; fetal hypoxia; placental dysfunction; fetal prostaglandin metabolism; and action of ethanol on developing neurons in the fetal brain, including the hippocampus, one of ethanol's main target sites. The effect of ethanol on the release of L-glutamate, an excitatory amino acid neurotransmitter, in the fetal hippocampus is described, and the role of L-glutamate in ethanol teratogenesis involving the hippocampus is discussed. A novel mechanism for abnormal neuronal development in the fetal hippocampus produced by prenatal ethanol exposure is presented, and future experiments to test this hypothesis are proposed.Key words: ethanol neurobehavioural teratogenesis, fetal alcohol syndrome, hippocampus, L-glutamate.


Author(s):  
C. Uphoff ◽  
C. Nyquist-Battie

Fetal Alcohol Syndrone (FAS) is a syndrome with characteristic abnormalities resulting from prenatal exposure to ethanol. In many children with FAS syndrome gross pathological changes in the heart are seen with septal defects the most prevalent abnormality recorded. Few studies in animal models have been performed on the effects of ethanol on heart development. In our laboratory, it has been observed that prenatal ethanol exposure of Swiss albino mice results in abnormal cardiac muscle ultrastructure when mice were examined at birth and compared to pairfed and normal controls. Fig. 1 is an example of the changes that are seen in the ethanol-exposed animals. These changes include enlarged mitochondria with loss of inner mitochondrial membrane integrity and loss of myofibrils. Morphometric analysis substantiated the presence of these alterations from normal cardiac ultrastructure. The present work was undertaken to determine if the pathological changes seen in the newborn mice prenatally exposed to ethanol could be reversed with age and abstinence.


Author(s):  
Carmen Lopez-Arvizu ◽  
Carmel Bogle ◽  
Harolyn M.E. Belcher

Prenatal exposure to ethanol can result in a wide range of clinical presentations that are grouped under the term “Fetal Alcohol Spectrum Disorders” (FASD). The direct cellular teratogenic effects of ethanol on fetal neurodevelopment include damage to cell survival, proliferation, and migration mechanisms. Dysregulation of neurotransmission and alteration of genetic transcription have also been implicated in the neurotoxic effects of prenatal ethanol exposure. These deleterious events lead to brain volume reduction, corpus callosum dysgenesis, cerebellar, and other neuroanatomical anomalies that have been observed in individuals with FASD. Beyond direct ethanol-induced insults, the impact that ethanol has on maternal nutrition, metabolism, hormonal regulation, and placental physiology also adversely effects fetal development. The complex interactions between numerous neurobiological and psychosocial mechanisms that hinder optimal fetal neurodevelopment are reflected by the heterogeneous clinical presentation of FASD, including impaired growth, dysmorphic facial features, and cognitive and behavioral disorders.


1986 ◽  
Vol 25 (S2) ◽  
pp. 97-112 ◽  
Author(s):  
Kathleen K. Sulik ◽  
Malcolm C. Johnston ◽  
Paula A. Daft ◽  
William E. Russell ◽  
Deborah B. Dehart ◽  
...  

Alcohol ◽  
2009 ◽  
Vol 43 (2) ◽  
pp. 147-161 ◽  
Author(s):  
Audrey G. Marshall ◽  
Molly M. McCarthy ◽  
Kirk M. Brishnehan ◽  
Venugopal Rao ◽  
Lyn M. Batia ◽  
...  

2021 ◽  
Vol 22 (13) ◽  
pp. 7083
Author(s):  
Malgorzata Lopatynska-Mazurek ◽  
Lukasz Komsta ◽  
Ewa Gibula-Tarlowska ◽  
Jolanta H. Kotlinska

Fetal alcohol spectrum disorders (FASDs) are one of the most common consequences of ethanol exposure during pregnancy. In adulthood, these disorders can be manifested by learning and memory deficits and depressive-like behavior. Ethanol-induced oxidative stress may be one of the factors that induces FASD development. The mammalian target of the Rapamycin (mTOR) signaling pathway that acts via two distinct multiprotein complexes, mTORC1 and mTORC2, can affect oxidative stress. We investigated whether mTOR-dependent or mTOR-independent mechanisms are engaged in this phenomenon. Thus, Rapamycin—a selective inhibitor of mTORC1, Torin-2—a non-selective mTORC1/mTORC2 inhibitor, and FK-506—a drug that impacts oxidative stress in an mTOR-independent manner were used. Behavioral tests were performed in adult (PND60-65) rats using a passive avoidance (PA) task (aversive learning and memory) and forced swimming test (FST) (depressive-like behaviors). In addition, the biochemical parameters of oxidative stress, such as lipid peroxidation (LPO), as well as apurinic/apyrimidinic (AP)-sites were determined in the hippocampus and prefrontal cortex in adult (PND65) rats. The rat FASD model was induced by intragastric ethanol (5 g/kg/day) administration at postnatal day (PND)4–9 (an equivalent to the third trimester of human pregnancy). All substances (3 mg/kg) were given 30 min before ethanol. Our results show that neonatal ethanol exposure leads to deficits in context-dependent fear learning and depressive-like behavior in adult rats that were associated with increased oxidative stress parameters in the hippocampus and prefrontal cortex. Because these effects were completely reversed by Rapamycin, an mTORC1 inhibitor, this outcome suggests its usefulness as a preventive therapy in disorders connected with prenatal ethanol exposure.


F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1896 ◽  
Author(s):  
Tyler H. Reekes ◽  
H. Thomas Vinyard III ◽  
William Echols ◽  
Andrew J. Eubank III ◽  
Michael D. Bouldin ◽  
...  

Prenatal ethanol exposure can negatively affect development, causing physical and/or cognitive deficits in the offspring. Behavioral changes are typically characterized during childhood, but they can also persist into adulthood. The extent of Fetal Alcohol Spectrum Disorder (FASD) abnormalities depends upon the amount and manner of ethanol intake, leading to a large variety of animal models. In order to mimic the genetically diverse human condition, we examined an outbred strain of mice exposed to chronic gestational ethanol and characterized subsequent behavioral alterations during adulthood. To detect deficits in cognitive ability and/or motor function, we ran the mice through tests designed to detect either memory/learning ability or motor strength/skill. We tested cognitive responses using the Barnes Maze and the Open Field Aversion Test, and motor skills using Kondziela’s Inverted Screen Test and the rotarod. As adults, the FASD mice showed no significant differences on grip strength, open field, or the Barnes maze; however, we found that outbred mice who had experienced moderate prenatal ethanol exposure were slower to learn the rotarod as adults, though they did not differ in overall performance. Our data suggest a specific FASD vulnerability in motor learning ability, and also open the door to further investigation on the effect of ethanol on brain areas involved in motor learning, including the striatum.


2021 ◽  
Vol 14 ◽  
Author(s):  
Bonnie Alberry ◽  
Benjamin I. Laufer ◽  
Eric Chater-Diehl ◽  
Shiva M. Singh

Neurodevelopment in humans is a long, elaborate, and highly coordinated process involving three trimesters of prenatal development followed by decades of postnatal development and maturation. Throughout this period, the brain is highly sensitive and responsive to the external environment, which may provide a range of inputs leading to positive or negative outcomes. Fetal alcohol spectrum disorders (FASD) result from prenatal alcohol exposure (PAE). Although the molecular mechanisms of FASD are not fully characterized, they involve alterations to the regulation of gene expression via epigenetic marks. As in the prenatal stages, the postnatal period of neurodevelopment is also sensitive to environmental inputs. Often this sensitivity is reflected in children facing adverse conditions, such as maternal separation. This exposure to early life stress (ELS) is implicated in the manifestation of various behavioral abnormalities. Most FASD research has focused exclusively on the effect of prenatal ethanol exposure in isolation. Here, we review the research into the effect of prenatal ethanol exposure and ELS, with a focus on the continuum of epigenomic and transcriptomic alterations. Interestingly, a select few experiments have assessed the cumulative effect of prenatal alcohol and postnatal maternal separation stress. Regulatory regions of different sets of genes are affected by both treatments independently, and a unique set of genes are affected by the combination of treatments. Notably, epigenetic and gene expression changes converge at the clustered protocadherin locus and oxidative stress pathway. Functional studies using epigenetic editing may elucidate individual contributions of regulatory regions for hub genes and further profiling efforts may lead to the development of non-invasive methods to identify children at risk. Taken together, the results favor the potential to improve neurodevelopmental outcomes by epigenetic management of children born with FASD using favorable postnatal conditions with or without therapeutic interventions.


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