scholarly journals Early Ethanol Exposure Inhibits the Differentiation of Hippocampal Dentate Gyrus Granule Cells in a Mouse Model of Fetal Alcohol Spectrum Disorders

2020 ◽  
Vol 44 (5) ◽  
pp. 1112-1122
Author(s):  
Wenhua Xu ◽  
Hui Li ◽  
Caigu He ◽  
Jacqueline Frank ◽  
Gang Chen
Keyword(s):  
Mouse Model ◽  
Dentate Gyrus ◽  
Granule Cells ◽  
Fetal Alcohol Spectrum Disorders ◽  
Ethanol Exposure ◽  
Fetal Alcohol ◽  
Hippocampal Dentate Gyrus ◽  
Spectrum Disorders ◽  
Fetal Alcohol Spectrum

Neurobiology of Fetal Alcohol Spectrum Disorders

2017 ◽  
Author(s):  
Carmen Lopez-Arvizu ◽  
Carmel Bogle ◽  
Harolyn M.E. Belcher
Keyword(s):  
Hormonal Regulation ◽  
Maternal Nutrition ◽  
Fetal Alcohol Spectrum Disorders ◽  
Ethanol Exposure ◽  
Prenatal Ethanol Exposure ◽  
Fetal Alcohol ◽  
Wide Range ◽  
Spectrum Disorders ◽  
The Impact ◽  
Fetal Alcohol Spectrum

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.

scholarly journals Aversive Learning Deficits and Depressive-Like Behaviors Are Accompanied by an Increase in Oxidative Stress in a Rat Model of Fetal Alcohol Spectrum Disorders: The Protective Effect of Rapamycin

2021 ◽  
Vol 22 (13) ◽  
pp. 7083
Author(s):  
Malgorzata Lopatynska-Mazurek ◽  
Lukasz Komsta ◽  
Ewa Gibula-Tarlowska ◽  
Jolanta H. Kotlinska
Keyword(s):  
Oxidative Stress ◽  
Prefrontal Cortex ◽  
Learning And Memory ◽  
Fetal Alcohol Spectrum Disorders ◽  
Ethanol Exposure ◽  
Prenatal Ethanol Exposure ◽  
Aversive Learning ◽  
Fetal Alcohol ◽  
Spectrum Disorders ◽  
Fetal Alcohol Spectrum

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.

Maternal Oral Intake Mouse Model for Fetal Alcohol Spectrum Disorders: Ocular Defects as a Measure of Effect

2006 ◽  
Vol 30 (10) ◽  
pp. 1791-1798 ◽  
Author(s):  
Scott E. Parnell ◽  
Deborah B. Dehart ◽  
Tiffany A. Wills ◽  
Shao-yu Chen ◽  
Clyde W. Hodge ◽  
...  
Keyword(s):  
Mouse Model ◽  
Fetal Alcohol Spectrum Disorders ◽  
Oral Intake ◽  
Fetal Alcohol ◽  
Spectrum Disorders ◽  
Fetal Alcohol Spectrum

scholarly journals Ethanol Exposure Alters Protein Expression in a Mouse Model of Fetal Alcohol Spectrum Disorders

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Stephen Mason ◽  
Bruce Anthony ◽  
Xianyin Lai ◽  
Heather N. Ringham ◽  
Mu Wang ◽  
...  
Keyword(s):  
Embryo Culture ◽  
Triosephosphate Isomerase ◽  
Fetal Alcohol Spectrum Disorders ◽  
Alcohol Exposure ◽  
Nervous System Development ◽  
Ethanol Exposure ◽  
Fetal Alcohol ◽  
Whole Embryo Culture ◽  
Spectrum Disorders ◽  
Fetal Alcohol Spectrum

Alcohol exposure during development can result in variable growth retardation and facial dysmorphology known as fetal alcohol spectrum disorders. Although the mechanisms underlying the disorder are not fully understood, recent progress has been made that alcohol induces aberrant changes in gene expression and in the epigenome of embryos. To inform the gene and epigenetic changes in alcohol-induced teratology, we used whole-embryo culture to identify the alcohol-signature protein profile of neurulating C6 mice. Alcohol-treated and control cultures were homogenized, isoelectrically focused, and loaded for 2D gel electrophoresis. Stained gels were cross matched with analytical software. We identified 40 differentially expressed protein spots (P<0.01), and 9 spots were selected for LC/MS-MS identification. Misregulated proteins include serotransferrin, triosephosphate isomerase and ubiquitin-conjugating enzyme E2 N. Misregulation of serotransferrin and triosephosphate isomerase was confirmed with immunologic analysis. Alteration of proteins with roles in cellular function, cell cycle, and the ubiquitin-proteasome pathway was induced by alcohol. Several misregulated proteins interact with effectors of the NF-κB and Myc transcription factor cascades. Using a whole-embryo culture, we have identified misregulated proteins known to be involved in nervous system development and function.

scholarly journals Epigenetic Impacts of Early Life Stress in Fetal Alcohol Spectrum Disorders Shape the Neurodevelopmental Continuum

2021 ◽  
Vol 14 ◽  
Author(s):  
Bonnie Alberry ◽  
Benjamin I. Laufer ◽  
Eric Chater-Diehl ◽  
Shiva M. Singh
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Fetal Alcohol Spectrum Disorders ◽  
Early Life Stress ◽  
Ethanol Exposure ◽  
Prenatal Ethanol Exposure ◽  
Fetal Alcohol ◽  
Spectrum Disorders ◽  
Fetal Alcohol Spectrum

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.

Ethanol Effects on Cerebellar Myelination in a Postnatal Mouse Model of Fetal Alcohol Spectrum Disorders

Alcohol ◽  
2021 ◽  
Author(s):  
Victoria M. Niedzwiedz-Massey ◽  
James C. Douglas ◽  
Tonya Rafferty ◽  
Cynthia J.M. Kane ◽  
Paul D. Drew
Keyword(s):  
Mouse Model ◽  
Fetal Alcohol Spectrum Disorders ◽  
Fetal Alcohol ◽  
Spectrum Disorders ◽  
Fetal Alcohol Spectrum
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