Coordinated Tcf7l2 regulation in a mouse model implicates Wnt signaling in fetal alcohol spectrum disorders

2019 ◽  
Vol 97 (4) ◽  
pp. 375-379 ◽  
Author(s):  
Eric Chater-Diehl ◽  
Dustin Sokolowski ◽  
Bonnie Alberry ◽  
Shiva M. Singh
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Mouse Model ◽  
Wnt Signaling ◽  
Histone Modifications ◽  
Fetal Alcohol Spectrum Disorders ◽  
Alcohol Exposure ◽  
Fetal Alcohol ◽  
Spectrum Disorders ◽  
Fetal Alcohol Spectrum

Mouse models of fetal alcohol spectrum disorders (FASD) have repeatedly identified genes with long-term changes in expression, DNA methylation, noncoding RNA, and histone modifications in response to neurodevelopmental alcohol exposure. Articulation of FASD is achieved via alcohol’s effect on gene expression, likely involving epigenetic regulation. The list of genes affected is large and heterogeneous, depending on experimental protocol. We present reanalysis and synthesis of results highlighting the Wnt transcription factor 7 like 2 (Tcf7l2) gene as uniquely compatible with hippocampal DNA methylation, histone modifications, and gene expression changes in a coordinated response to neurodevelopmental alcohol exposure. We data-mined the literature for Tcf7l2 alterations in response to prenatal alcohol exposure. Four studies identified changes in brain Tcf7l2 expression in different FASD models. Further, we performed an in silico TCF7L2 binding site analysis for FASD mouse model data sets. Seven of these published gene lists were significantly enriched for TCF7L2 binding, indicating potential functional relationships. Finally, TCF7L2 is involved in regulation of hundreds of genes, with a role in brain development, myelination, and neuronal function. Tcf7l2 may be involved in neurological defects associated with alcohol exposure via dysregulation of many genes through Wnt signaling. Further functional work is warranted to validate this model for FASD.

scholarly journals Language Development Disorder in Fetal Alcohol Spectrum Disorders (FASD), a Case Study

Languages ◽  
2020 ◽  
Vol 5 (4) ◽  
pp. 37
Author(s):  
Yuri E. Vega-Rodríguez ◽  
Elena Garayzabal-Heinze ◽  
Esther Moraleda-Sepúlveda
Keyword(s):  
Fetal Alcohol Spectrum Disorders ◽  
Early Stage ◽  
Alcohol Exposure ◽  
Fetal Alcohol ◽  
Foster Home ◽  
Language Development Disorder ◽  
Spectrum Disorders ◽  
And Behavior ◽  
Fetal Alcohol Spectrum

Prenatal alcohol exposure can cause developmental damage in children. There are different types and ranges of alterations that fall under the name of fetal alcohol spectrum disorders (FASD). Disabilities in learning, cognition, and behavior are observed. Environmental conditions are an influencing factor in this population since they are generally adverse and are either not diagnosed at an early stage or given the appropriate support and approach. We present a case study of a 9-year-old child, in which all the variables affecting his development (FASD diagnosis and socioenvironmental conditions) were observed and analyzed. His early childhood under institutional care, the move to a foster home at the age of 6, and several measures of evaluation from foster care to the present are described. Difficulties in vocabulary, access to vocabulary, morphology, syntax, grammar, oral narrative, pragmatics, speech, and communication were observed, along with cognitive difficulties in memory, perception and executive functioning, social adaptation, learning, and behavior. An early diagnosis and approach enable this population to develop skills in different dimensions to address early adversity despite their neurological and behavioral commitment. Speech-language pathologist services are crucial for the diagnosis and treatment of the language and communication difficulties that characterize this syndrome.

scholarly journals Screening in treatment programs for Fetal Alcohol Spectrum Disorders that could affect therapeutic progress

2013 ◽  
Vol 2 (3) ◽  
pp. 37-49 ◽  
Author(s):  
Therese M Grant ◽  
Natalie Novick Brown ◽  
J. Christopher Graham ◽  
Nancy Whitney ◽  
Dan Dubovsky ◽  
...  
Keyword(s):  
Life History ◽  
Fetal Alcohol Spectrum Disorders ◽  
Prenatal Alcohol Exposure ◽  
Cognitive Impairments ◽  
Alcohol Exposure ◽  
Treatment Programs ◽  
Fetal Alcohol ◽  
Prenatal Alcohol ◽  
Spectrum Disorders ◽  
Fetal Alcohol Spectrum

Grant, T., Novick Brown, N., Graham, J., Whitney, N., Dubovsky, D. , & Nelson, L. (2013). Screening in treatment programs for Fetal Alcohol Spectrum Disorders that could affect therapeutic progress. The International Journal Of Alcohol And Drug Research, 2(3), 37-49. doi:10.7895/ijadr.v2i3.116 (http://dx.doi.org/10.7895/ijadr.v2i3.116)Aims: While structured intake interviews are the standard of care in substance abuse treatment programs, these interviews often do not screen for cognitive impairments, such as those found in fetal alcohol spectrum disorders (FASD) and other brain-based developmental disorders. The research reported here supports a brief interview protocol, the Life History Screen (LHS), that screens clients unobtrusively for adverse life-course outcomes typically found in FASD, so as to guide follow-up assessments and treatment planning.Design: Two-group observational study.Setting: A three-year case management intervention program in Washington State for high-risk women who abuse alcohol and/or drugs during pregnancy.Participants: Group 1: No prenatal alcohol exposure (N = 463); Group 2: Diagnosed with FASD (Fetal Alcohol Syndrome, Alcohol Related Neurodevelopmental Disorder, fetal alcohol effects, or static encephalopathy) by a qualified physician (N = 25), or suspected of having FASD (reported prenatal alcohol exposure and displayed behaviors consistent with a clinical diagnosis of FASD) (N = 61).Measures: The Addiction Severity Index (ASI) was administered to participants at intake. We analyzed eleven ASI items that corresponded to questions on the LHS in order to assess the potential of the LHS for identifying adults with possible FASD. The Life History Screen itself was not administered.Findings: Analysis of group differences between the diagnosed FASD and suspected FASD groups supported our decision to collapse the two groups for the main analysis. The Life History Screen shows promise as an efficient pre-treatment screen, in that core items are significantly associated with FASD group membership on factors involving childhood history, maternal drinking, education, substance use, employment, and psychiatric symptomatology.Conclusions: The Life History Screen may have utility as a self-report measure that can be used at the outset of treatment to identify clients with cognitive impairments and learning disabilities due to prenatal alcohol exposure.

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