Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome
| Autor: | Greetje Vande Velde, Neus Martínez-Abadías, Mara Dierssen, Alejandro González, Julia Albaigès, Xavier Sevillano, Rafael de la Torre, Sergi Llambrich, John M. Starbuck, Rubèn Gonzàlez, Jens Wouters, Anna Sarlé, James Sharpe |
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| Přispěvatelé: | Universitat Ramon Llull. La Salle, University of Central Florida, Indiana University Robert H. McKinney School of Law, MoSAIC, Universitat de Barcelona, Barcelona Institute for Science and Technology, Universitat Pompeu Fabra, CIBERER, ICREA, European Molecular Biology Laboratory, IMIM-Hospital del Mar Medical Research Institute, CIBERobn |
| Rok vydání: | 2020 |
| Předmět: |
Male
Genètica -- Innovacions tecnològiques Down syndrome Physiology Diseases Catechin Mice Te verd Child Te 61 - Medicina Multidisciplinary food and beverages Skeleton (computer programming) medicine.anatomical_structure Child Preschool Medicine Female 62 - Enginyeria. Tecnologia Adolescent Science complex mixtures Chromosomes Article 00 - Ciència i coneixement. Investigació. Cultura. Humanitats medicine Animals Humans Facial development Mastication Tea business.industry Plant Extracts Infant Translational research Down Síndrome de medicine.disease Green tea Cromosomes Malformacions -- Aspectes genètics Disease Models Animal Face Síndrome de Down Dietary Supplements Facial skeleton Genètica -- Investigació Down Syndrome business Trisomy Chromosome 21 |
| Zdroj: | Scientific Reports RECERCAT (Dipòsit de la Recerca de Catalunya) Recercat: Dipósit de la Recerca de Catalunya Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) Dipòsit Digital de la UB Universidad de Barcelona Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) Recercat. Dipósit de la Recerca de Catalunya instname |
| ISSN: | 2045-2322 |
| Popis: | Trisomy 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. We acknowledge support from a 2016 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation IN[16]_CMA_BIO_0096 (NMA). We also acknowledge grant support from the following: CRG Awards for Collaborative Research Proposals, CRG Awards 2015-005822 (NMA, JA), Marguerite-Marie Delacroix Foundation fellowship (SL), Jerome Lejeune Foundation, #1782 (GVV, NMA), University of Central Florida start-up funds (JMS), American Association of Physical Anthropologists Professional Development Program Grant (JMS), Flemish Research Foundation (FWO) fellowship (GVV), and KU Leuven IF STG/15/024 (GVV), MINECO SAF2016-79956-R (MD), and the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013–2017’, SEV-2012-0208 |
| Databáze: | OpenAIRE |
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