Notch signaling pathway inhibitor DAPT improves alcohol-induced neuronal differentiation impairment in zebrafish / 南方医科大学学报

OBJECTIVE@#To explore the role of the Notch signaling pathway in regulating neuronal differentiation and sensorimotor ability in a zebrafish model of fetal alcohol spectrum disorder.@*METHODS@#Zebrafish embryos treated with DMSO or 50 μmol/L DAPT (a Notch signaling pathway inhibitor) were examined for mortality rate, hatching rate, malformation rate, and body length at 15 days post fertilization (dpf). The mRNA expression levels of sox2, neurogenin1 and huc in the treated zebrafish embryos were detected using in situ hybridization and qRT-PCR, and their behavioral responses to strong light and vibration stimulation were observed. The zebrafish embryos were then exposed to DMSO, 1.5% ethanol, DAPT, or both ethanol and DAPT, and the changes in mRNA expression levels of sox2, neurogenin1, huc, and the Notch signaling pathway genes as well as behavioral responses were evaluated.@*RESULTS@#Exposure to 50 μmol/L DAPT significantly increased the mortality rate of 1 dpf zebrafish embryos (P < 0.01), decreased the hatching rate of 2 dpf embryos (P < 0.01), increased the malformation rate of 3 dpf embryos (P < 0.001), and reduced the body length of 15 dpf embryos (P < 0.05). DAPT treatment significantly downregulated sox2 mRNA expression (P < 0.01) and increased neurogenin1 (P < 0.05) and huc (P < 0.01) mRNA expressions in zebrafish embryos. The zebrafish with DAPT treatment exhibited significantly shortened movement distance (P < 0.001) and lowered movement speed (P < 0.05) in response to all the stimulation conditions. Compared with treatment with 1.5% ethanol alone, which obviously upregulated notch1a, her8a and NICD mRNA expressions in zebrafish embryos (P < 0.05), the combined treatment with ethanol and DAPT significantly increased neurogenin1 and huc mRNA expression, decreased sox2 mRNA expression (P < 0.01), and increased the moving distance and moving speed of zebrafish embryos in response to strong light stimulation (P < 0.05).@*CONCLUSION@#Ethanol exposure causes upregulation of the Notch signaling pathway and impairs neuronal differentiation and sensorimotor ability of zebrafish embryos, and these detrimental effects can be lessened by inhibiting the Notch signaling pathway.

Narrativa oral de indivíduos com Transtorno do Espectro Alcoólico Fetal / Oral narrative of individuals with Fetal Alcohol Spectrum Disorder

RESUMO Objetivo Investigar e comparar a narrativa oral de indivíduos com Transtorno do Espectro Alcoólico Fetal (TEAF) e de indivíduos com desenvolvimento típico de linguagem (DTL) e correlacionar o desempenho na narrativa oral com a pontuação do "4-Digit Diagnostic Code". Método Participaram 20 indivíduos com TEAF, de ambos os gêneros, com idade cronológica entre seis e 16 anos e 20 indivíduos com DTL, semelhantes quanto ao gênero, idade e nível socioeconômico aos do grupo TEAF. A narrativa oral foi eliciada por meio do livro "Frog, where are you?" e analisada quanto aos aspectos macroestruturais, microestruturais e nível de coerência global. Os aspectos macroestruturais incluíram elementos típicos de história e os microestruturais incluíram palavras (total, palavras diferentes), unidades comunicativas (C-Units), diversidade lexical e extensão média dos C-Units. Resultados Desempenho inferior foi encontrado para o grupo TEAF em todos os aspectos macroestruturais, exceto para os marcadores linguísticos. Dentre os aspectos microestruturais, a diversidade lexical e a ocorrência de "C-Units" incompletos foram aspectos que diferenciaram os grupos TEAF e DTL. O grupo TEAF apresentou nível de coerência global inferior ao grupo DTL. Correlações negativas foram encontradas entre os aspectos macroestruturais e os itens características faciais e alterações no Sistema Nervoso Central. Conclusão O uso restrito de elementos estruturais típicos de história com níveis inferiores de coerência e vocabulário reduzido diferenciaram o TEAF do DTL. Estudos futuros poderão explorar se a associação entre o desempenho narrativo e os itens do "4-Digit Diagnostic Code" apresentam valor preditivo no desempenho narrativo dos indivíduos com TEAF.

ABSTRACT Purpose To investigate and compare the oral narrative of individuals with FASD and individuals with typical language development (TLD), as well as to correlate the narrative performance with the score from 4-Digit Diagnostic Code. Methods Participants were 20 individuals with FASD, of both genders, with chronological age between 6 and 16 years, and 20 individuals with TLD, same gender and similar to the FASD group in age and socioeconomic status. The oral narrative was elicited using the book Frog, where are you? and the data were analyzed in terms of macrostructure, microstructure and global coherence level. Measures regarding the macrostructure included the presence of typical structural elements of storytelling, while the microstructural aspects included words (total and different words), communication units (C-Units), lexical diversity, and mean length of C-Units. Results Low performance was found in the FASD group for all macrostructural aspects, with the exception of linguistic markers. Among the microstructural aspects, lexical diversity and incomplete C-Units were different between the FASD and TLD groups. The FASD group presented lower global coherence level compared to the TLD group. Negative correlations were found between macrostructural aspects, facial characteristics, and Central Nervous System impairment. Conclusion Restricted use of typical structural elements of storytelling with lower levels of coherence and reduced vocabulary distinguished the FASD from the TDL group. Future studies may explore whether the association between narrative performance and the 4-Digit Diagnostic Code items present predictive values in the narrative performance of individuals with FASD.

Exposição pré-natal ao etanol: toxicidade, biomarcadores e métodos de detecção / Prenatal exposure to ethanol: toxicity, biomarkers and detection methods

CONTEXTO: A exposição pré-natal ao etanol pode produzir diversos efeitos adversos no desenvolvimento fetal denominados doença espectral do alcoolismo fetal (DEAF). A detecção precoce de exposição ao etanol permite que medidas preventivas sejam tomadas para minimizar os efeitos adversos da exposição. OBJETIVOS: O presente trabalho teve como objetivo revisar os principais efeitos tóxicos do etanol no neonato e os biomarcadores de exposição ao álcool. MÉTODOS: Foi realizada uma pesquisa bibliográfica na base de dados PubMed utilizando os descritores "effects maternal ethanol exposure" e "biomarkers ethanol prenatal exposure", além de referências cruzadas dos artigos selecionados. RESULTADOS: Diversos efeitos adversos no desenvolvimento fetal têm sido descritos, especialmente os prejuízos no sistema nervoso central. Os biomarcadores de exposição mais citados na literatura são os etil ésteres de ácidos graxos (EEAG), etil glicuronídeo (EtG) e etil sulfato (EtS) utilizando mecônio e cabelo como matriz biológica. CONCLUSÃO: A detecção precoce de exposição ao álcool na vida intrauterina pode ser realizada e é um instrumento para prevenir efeitos secundários, porque possibilita a intervenção farmacológica e educacional na criança com DEAF.

BACKGROUND: Prenatal exposure to ethanol can produce a complex set of effects on fetal development, which is denominated fetal alcohol spectrum disorder (FASD). Early detection of ethanol exposure can allow the prevention of some relevant adverse effects associated to FASD. OBJECTIVES: The aim of this work was to review the main toxic effects of ethanol on the neonate and the available biomarkers of prenatal alcohol exposure. METHODS: A bibliographic search was performed in PubMed employing the terms "effects maternal ethanol exposure" and "biomarkers ethanol prenatal exposure" and cross references. RESULTS: Many adverse effects on fetal development were described, especially deficits in the central nervous system. The biomarkers of ethanol exposure more widely described were fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG) and ethyl sulphate (EtS), being meconium and hair the most common biological matrices for laboratorial evaluation. DISCUSSION: The early detection of alcohol exposure in intra-uterine life is useful to prevent the secondary effects of FASD through pharmacologic and educational intervention in affected children.

Fetal alcohol spectrum disorder(FASD).

Fetal alcohol syndrome (FAS)is the leading cause of mental retardation worldwide but is also the foremost preventable cause of neurobehavioral and developmental abnormalities. It is equally important to know spectrum of disorders due to maternal alcoholism during pregnancy such as Fetal alcohol spectrum disorder (FASD)in order to identify and treat affected child and family effectively.This article aims to create awareness among practising clinicians most of whom are only aware of phenotypical variant of FASD which is FAS.In this article we discuss those aspects of FASD relevant to the clinician such as: terminological ambiguity, assessment, diagnosis and prevention.

The First Report of Fetal Alcohol Effect in a 12 Year-Old Child in Korea

We present the first report of fetal alcohol effect in a 12 year-old child in Korea. The mother had consumed 162 g of alcohol per week continuously during pregnancy. His first febrile seizure occurred before he was 1 year old, and became more frequent 2 years later. He started showing signs of right paraplegia when he was 3.5 years old and brain MRI revealed periventricular leucomalacia near the left ventricle. He was microcephalic and his growth was retarded. He was irritable, impatient, impulsive, and inattentive, and showed disinterest in school activities and aggressive and dangerous behavior. After the diagnosis of attention deficit/hyperactivity disorder was made, psychopharmacological treatment and family support was initiated. After 10 months, he still had intermittent ideas of reference, although the aggressive behavior, inattentiveness, and impulsivity had improved. Using this case study, we stress the importance of maternal alcohol history in patients with these characteristics.

An Introduction to Screening Instruments and Diagnostic Criteria for Fetal Alcohol Spectrum Disorder / 中国临床心理学杂志

The adverse effects of alcohol on the developing human represent a spectrum of structural disabilities,most accurately termed Fetal Alcohol Spectrum Disorder(FASD).Patients at the severe end of spectrum(with complete phenotype) have been defined as having the Fetal Alcohol Syndrome.In China there are increasingly more female people who drink alcohol,which results in a higher potential risk of FASD.Screening and diagnosing FASD among children and adults presented Chinese physicians and researchers with a big challenge.Introducing the screening instruments and diagnostic criteria developed by western countries would contribute to the study of FASD in China.