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

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...

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Authors: Llambrich, Sergi, González, Rubén, Albaigès-Ràfols, Júlia, Wouters, Jens, Marain, Fopke, Himmelreich, Uwe, Sharpe, James, Dierssen, Mara, Gsell, Willy, Martínez Abadías, Neus, Velde, Greetje Vande
Format: article
Status:Published version
Publication Date:2022
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/52837
Online Access:http://hdl.handle.net/10230/52837
http://dx.doi.org/10.3389/fmed.2022.815739
Access Level:Open access
Keyword:Down, Síndrome de
Malalties congènites
Cervell
Crani
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spelling Multimodal in vivo imaging of the integrated postnatal development of brain and skull and its co-modulation With neurodevelopment in a down syndrome mouse modelLlambrich, SergiGonzález, RubénAlbaigès-Ràfols, JúliaWouters, JensMarain, FopkeHimmelreich, UweSharpe, JamesDierssen, MaraGsell, WillyMartínez Abadías, NeusVelde, Greetje VandeDown, Síndrome deMalalties congènitesCervellCraniThe 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.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 SLFrontiers Media202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/52837http://dx.doi.org/10.3389/fmed.2022.815739reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglés© 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 termshttps://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/528372026-05-29T05:05:01Z
dc.title.none.fl_str_mv 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
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
spellingShingle 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
Llambrich, Sergi
Down, Síndrome de
Malalties congènites
Cervell
Crani
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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.creator.none.fl_str_mv Llambrich, Sergi
González, Rubén
Albaigès-Ràfols, Júlia
Wouters, Jens
Marain, Fopke
Himmelreich, Uwe
Sharpe, James
Dierssen, Mara
Gsell, Willy
Martínez Abadías, Neus
Velde, Greetje Vande
author Llambrich, Sergi
author_facet Llambrich, Sergi
González, Rubén
Albaigès-Ràfols, Júlia
Wouters, Jens
Marain, Fopke
Himmelreich, Uwe
Sharpe, James
Dierssen, Mara
Gsell, Willy
Martínez Abadías, Neus
Velde, Greetje Vande
author_role author
author2 González, Rubén
Albaigès-Ràfols, Júlia
Wouters, Jens
Marain, Fopke
Himmelreich, Uwe
Sharpe, James
Dierssen, Mara
Gsell, Willy
Martínez Abadías, Neus
Velde, Greetje Vande
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Down, Síndrome de
Malalties congènites
Cervell
Crani
topic Down, Síndrome de
Malalties congènites
Cervell
Crani
description 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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/52837
http://dx.doi.org/10.3389/fmed.2022.815739
url http://hdl.handle.net/10230/52837
http://dx.doi.org/10.3389/fmed.2022.815739
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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