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Title: Green tea extracts containing Epigallocatechin-3-Gallate modulate facial development in Down syndrome
Author: Starbuck, John M.
Llambrich, Sergi
González, Rubén
Albaigès, Júlia
Sarlé, Anna
Wouters, Jens
González, Alejandro
Sevillano, Xavier
Sharpe, James
De la Torre, Rafael
Dierssen, Mara
Vande Velde, Greetje
Martínez Abadías, Neus, 1978-
Keywords: Cromosomes
Síndrome de Down
Down syndrome
Issue Date: 25-Feb-2021
Publisher: Nature Publishing Group
Abstract: risomy of human chromosome 21 (Down syndrome, DS) alters development of multiple organ systems, including the face and underlying skeleton. Besides causing stigmata, these facial dysmorphologies can impair vital functions such as hearing, breathing, mastication, and health. To investigate the therapeutic potential of green tea extracts containing epigallocatechin-3-gallate (GTE-EGCG) for alleviating facial dysmorphologies associated with DS, we performed an experimental study with continued pre- and postnatal treatment with two doses of GTE-EGCG supplementation in a mouse model of DS, and an observational study of children with DS whose parents administered EGCG as a green tea supplement. We evaluated the effect of high (100 mg/kg/day) or low doses (30 mg/kg/day) of GTE-EGCG, administered from embryonic day 9 to post-natal day 29, on the facial skeletal development in the Ts65Dn mouse model. In a cross-sectional observational study, we assessed the facial shape in DS and evaluated the effects of self-medication with green tea extracts in children from 0 to 18 years old. The main outcomes are 3D quantitative morphometric measures of the face, acquired either with micro-computed tomography (animal study) or photogrammetry (human study). The lowest experimentally tested GTE-EGCG dose improved the facial skeleton morphology in a mouse model of DS. In humans, GTE-EGCG supplementation was associated with reduced facial dysmorphology in children with DS when treatment was administered during the first 3 years of life. However, higher GTE-EGCG dosing disrupted normal development and increased facial dysmorphology in both trisomic and euploid mice. We conclude that GTE-EGCG modulates facial development with dose-dependent effects. Considering the potentially detrimental effects observed in mice, the therapeutic relevance of controlled GTE-EGCG administration towards reducing facial dysmorphology in young children with Down syndrome has yet to be confirmed by clinical studies.
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It is part of: Scientific Reports, 2021, vol. 11, num. 4715
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ISSN: 2045-2322
Appears in Collections:Articles publicats en revistes (Biologia Evolutiva, Ecologia i Ciències Ambientals)

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