Multimodal in vivo imaging of the integrated postnatal development of brain and skull and its co-modulation With neurodevelopment in a down syndrome mouse model

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• dc.contributor.author Llambrich, Sergi
• dc.contributor.author González, Rubén
• dc.contributor.author Albaigès-Ràfols, Júlia
• dc.contributor.author Wouters, Jens
• dc.contributor.author Marain, Fopke
• dc.contributor.author Himmelreich, Uwe
• dc.contributor.author Sharpe, James
• dc.contributor.author Dierssen, Mara
• dc.contributor.author Gsell, Willy
• dc.contributor.author Martínez Abadías, Neus
• dc.contributor.author Velde, Greetje Vande
• dc.date.accessioned 2022-04-07T06:10:08Z
• dc.date.available 2022-04-07T06:10:08Z
• dc.date.issued 2022
• dc.description.abstract The brain and skeletal systems are intimately integrated during development through common molecular pathways. This is evidenced by genetic disorders where brain and skull dysmorphologies are associated. However, the mechanisms underlying neural and skeletal interactions are poorly understood. Using the Ts65Dn mouse model of Down syndrome (DS) as a case example, we performed the first longitudinal assessment of brain, skull and neurobehavioral development to determine alterations in the coordinated morphogenesis of brain and skull. We optimized a multimodal protocol combining in vivo micro-computed tomography (μCT) and magnetic resonance imaging (μMRI) with morphometric analyses and neurodevelopmental tests to longitudinally monitor the different systems' development trajectories during the first postnatal weeks. We also explored the impact of a perinatal treatment with green tea extracts enriched in epigallocatechin-3-gallate (GTE-EGCG), which can modulate cognition, brain and craniofacial development in DS. Our analyses quantified alterations associated with DS, with skull dysmorphologies appearing before brain anomalies, reduced integration and delayed acquisition of neurodevelopmental traits. Perinatal GTE-EGCG induced disparate effects and disrupted the magnitude of integration and covariation patterns between brain and skull. Our results exemplify how a longitudinal research approach evaluating the development of multiple systems can reveal the effect of morphological integration modulating the response of pathological phenotypes to treatment, furthering our understanding of complex genetic disorders.
• dc.description.sponsorship This research was funded by research grants from CRG Awards BrainFace, the Jerome Lejeune Foundation (3M180477), KU Leuven BOF (C24/17/061 and STG/15/024), Grup de Recerca Consolidat en Antropologia Biològica, GREAB (2017 SGR 1630) and a 2-year doctoral fellowship from the Marie-Marguerite Delacroix Foundation to SL
• dc.format.mimetype application/pdf
• dc.identifier.citation Llambrich S, González R, Albaigès J, Wouters J, Marain F, Himmelreich U et al. Multimodal in vivo imaging of the integrated postnatal development of brain and skull and its co-modulation With neurodevelopment in a down syndrome mouse model. Front Med (Lausanne). 2022 Feb 11;9:815739. DOI: 10.3389/fmed.2022.815739
• dc.identifier.doi http://dx.doi.org/10.3389/fmed.2022.815739
• dc.identifier.issn 2296-858X
• dc.identifier.uri http://hdl.handle.net/10230/52837
• dc.language.iso eng
• dc.publisher Frontiers Media
• dc.rights © 2022 Sergi Llambrich et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.other Down, Síndrome de
• dc.subject.other Malalties congènites
• dc.subject.other Cervell
• dc.subject.other Crani
• dc.title Multimodal in vivo imaging of the integrated postnatal development of brain and skull and its co-modulation With neurodevelopment in a down syndrome mouse model
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion