scholarly journals Transcriptomic changes due to early, chronic intermittent alcohol exposure during forebrain development implicate WNT signaling, cell‐type specification, and cortical regionalization as primary determinants of fetal alcohol syndrome

Author(s):  
Máté Fischer ◽  
Praveen Chander ◽  
Huining Kang ◽  
Nikolaos Mellios ◽  
Jason P. Weick
2019 ◽  
Author(s):  
Máté Fischer ◽  
Praveen Chander ◽  
Huining Kang ◽  
Jason P. Weick

AbstractFetal alcohol spectrum disorders (FASD) are described by a cluster of deficits following in utero alcohol exposure, whose effects disproportionately target the cerebral cortex. In vitro and in vivo models of FASD have successfully recapitulated multiple facets of clinical presentations, including morphological and behavioral deficits, but far less is understood regarding the molecular and genetic bases of FASD. In this study, we utilize an in vitro human pluripotent stem cell-based (hPSC) model of corticogenesis to probe the effect of early, chronic alcohol exposure on the transcriptome of developing cortical neurons. We here identify a relatively limited number of significantly altered biological pathways, including regional patterning, cell-type specification, axon guidance and synaptic function. Significant upregulation of WNT signaling-related transcripts, to the exclusion of other secreted morphogens was also observed in alcohol exposed cultures. Lastly, an overall alcohol-associated shift towards an increased caudal profile, at the expense of rostral molecular identity was observed, representing a potentially previously underappreciated FASD phenotype.


2001 ◽  
Vol 7 (5) ◽  
pp. 648-649 ◽  
Author(s):  
Paul D. Connor

The primary focus of this volume is on the impact of alcohol on brain development. It is a perfect example of how research on both animals and humans can interact to produce very important findings. In the case of prenatal alcohol exposure, dialogue between animal and human researchers has proved to be very profitable for both lines of research. Initial observations by human researchers identified a syndrome of facial stigmata, physical malformations, and early behavioral disturbances that was related to maternal alcohol abuse during pregnancy. They gave this syndrome the name Fetal Alcohol Syndrome. However, human researchers were unable to state unequivocally that prenatal alcohol exposure was teratogenic to the fetus. Thus, they turned to animal researchers who were able to model Fetal Alcohol Syndrome in a variety of animals and to confirm the teratogenicity of alcohol on the developing fetus. The quarter century of studies of the damage caused by prenatal alcohol exposure is replete with such interactions between these two groups of researchers. Without the input and pioneering studies of animal researchers on the effects of prenatal alcohol exposure, human researchers would have much less understanding of the damage caused by alcohol exposure in utero or insights into possible treatment or remediation strategies for those damaged by alcohol exposure.


2004 ◽  
Vol 39 (6) ◽  
pp. 503-508 ◽  
Author(s):  
NATHANIEL C. O. KHAOLE ◽  
VIJAY A. RAMCHANDANI ◽  
DENIS L. VILJOEN ◽  
TING-KAI LI

2015 ◽  
Vol 25 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Christopher Bolinger ◽  
James Dembowski

Speech of children with fetal alcohol syndrome (FAS) has been little studied compared to language. Becker, Warr-Leeper, and Leeper (1990), found a relationship between prenatal alcohol exposure, oral motor control, and speech articulation. Behavioral tests suggest deficits in focal oral motor control specific to children with FAS (Bolinger & Dembowski, 2010). The current project extends that investigation through acoustic measures. Peak and mean frequencies of stop consonant releases were used to infer control of place of articulation. Voice onset time (VOT) was used to infer articulatory-laryngeal coordination. Preliminary measures on 3 experimental speakers and 2 matched neurotypical controls suggest higher stop consonant frequencies in the experimental group, with a poorer distinction between alveolar and velar stops than in the control group. Voiced VOT values were significantly longer for FAS children than for controls. Mean voiceless VOTs were similar across groups, but substantially more variable for the FAS children. Values may be interpreted as acoustic evidence for specific speech motor control deficits in FAS children relative to matched neurotypical children.


1997 ◽  
Vol 131 (5) ◽  
pp. 718-721 ◽  
Author(s):  
Sarah N. Mattson ◽  
Edward P. Riley ◽  
Laura Gramling ◽  
Dean C. Delis ◽  
Kenneth Lyons Jones

PEDIATRICS ◽  
1992 ◽  
Vol 89 (1) ◽  
pp. 67-77
Author(s):  
Susan J. Astley ◽  
Sterling K. Clarren ◽  
Ruth E. Little ◽  
Paul D. Sampson ◽  
Janet R. Daling

The association between fetal marijuana and/or alcohol exposure and facial features resembling fetal alcohol syndrome was investigated in a sample of 80 children. Standardized lateral and frontal facial photographs were taken of 40 children, 5 to 7 years of age, whose mothers reported frequent use of marijuana during the first trimester of pregnancy and 40 children whose mothers reported no use of marijuana during pregnancy. The marijuana-exposed and unexposed children were group-matched on alcohol exposure prior to and during pregnancy, sex, race, and age at the time of assessment. The photographs were assessed clinically by a study staff dysmorphologist and morphometrically by computerized landmark analysis. Fetal alcohol syndrome-like facial features were not associated with prenatal marijuana exposure in this study sample. No consistent patterns of facial features were identified among the marijuana-exposed group. Maternal consumption of two or more ounces of alcohol per day, on average, in early gestation was found to be associated with fetal alcohol syndrome-like facial features identified both clinically and morphometrically. Cocaine use reported by 13 of the 80 women was independently associated with mild facial dysmorphic features of hypertelorism and midfacial flattening. The results demonstrate the usefulness of this diagnostic technique for quantifying anomalies apparently unique to fetal alcohol syndrome and for targeting clusters of anomalies in new conditions for future evaluation.


2018 ◽  
Vol 14 (3) ◽  
pp. 214-223
Author(s):  
Katarzyna Ludwików ◽  
Konrad Małkiewicz

The fetal alcohol syndrome (FAS) is a syndrome of congenital somatic and neurological defects occurring in children of mothers who drank alcohol during their pregnancy. Both ethanol and its main metabolite, acetic aldehyde cause developmental disorders in the fetus. The full spectrum FAS includes characteristic abnormalities in the structure of the facial skeleton, height and weight deficits as well as damage in the structure and functions of the central nervous system. The FAS is an incurable disorder and the most severe one among developmental disorders resulting from prenatal exposure to alcohol. In Poland, according to the estimates of Państwowa Agencja Rozwiązywania Problemów Alkoholowych (PARPA) - the State Agency for Prevention of Alcohol-Related Problems, three in a thousand of live births may be affected by the FAS. So far, an alcohol dose that would be safe for the fetus has not been determined and any quantity poses a risk of disturbances in a child’s development. <b>Aim.</b> This paper is aimed at getting to know better the problems of the Fetal Alcohol Syndrome, presentation of its symptoms and diagnostic methods based on an analysis of available literature. <b>Material and methods.</b> A literature review was conducted based on the following databases: PubMed, Scopus, Dentistry & Oral Sciences Source, Polska Bibliografia Lekarska /Polish Medical Bibliography/, with the use of the key words: FAS, fetal alcohol syndrome, facial abnormalities, prenatal alcohol exposure. For analysis, 35 papers published in the years 1968-2016 in the Polish and English languages were selected. <b>Conclusions.</b> Although for the diagnostics of the fetal alcohol syndrome in Poland a four-digit diagnostic code is applied, the FAS continues to represent a difficult diagnostic challenge and its correct diagnosis requires collaboration of physicians in numerous medical specialties.


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