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Research ArticleNew Research, Disorders of the Nervous System

Combined Treatment With Environmental Enrichment and (-)-Epigallocatechin-3-Gallate Ameliorates Learning Deficits and Hippocampal Alterations in a Mouse Model of Down Syndrome

Silvina Catuara-Solarz, Jose Espinosa-Carrasco, Ionas Erb, Klaus Langohr, Juan Ramon Gonzalez, Cedric Notredame and Mara Dierssen
eNeuro 19 October 2016, 3 (5) ENEURO.0103-16.2016; DOI: https://doi.org/10.1523/ENEURO.0103-16.2016
Silvina Catuara-Solarz
1Cellular and Systems Neurobiology, Systems Biology Program, the Barcelona Institute of Science and Technology, Centre for Genomic Regulation (CRG), 08003, Barcelona, Spain
2Universitat Pompeu Fabra (UPF), Barcelona, 08003, Spain
3Human Pharmacology and Clinical Neurosciences Research Group, Neurosciences Research Program, Hospital Del Mar Medical Research Institute (IMIM), Barcelona, 08003, Spain
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Jose Espinosa-Carrasco
1Cellular and Systems Neurobiology, Systems Biology Program, the Barcelona Institute of Science and Technology, Centre for Genomic Regulation (CRG), 08003, Barcelona, Spain
2Universitat Pompeu Fabra (UPF), Barcelona, 08003, Spain
4Comparative Bioinformatics, Bioinformatics, and Genomics Program, Barcelona Institute of Science and Technology, Centre for Genomic Regulation, Barcelona, 08003, Spain
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Ionas Erb
2Universitat Pompeu Fabra (UPF), Barcelona, 08003, Spain
4Comparative Bioinformatics, Bioinformatics, and Genomics Program, Barcelona Institute of Science and Technology, Centre for Genomic Regulation, Barcelona, 08003, Spain
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Klaus Langohr
3Human Pharmacology and Clinical Neurosciences Research Group, Neurosciences Research Program, Hospital Del Mar Medical Research Institute (IMIM), Barcelona, 08003, Spain
5Department of Statistics and Operations Research, Universitat Politècnica De Catalunya/BarcelonaTech, Barcelona, 08034, Spain
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Juan Ramon Gonzalez
6Centre for Research in Environmental Epidemiology, Barcelona, 08003, Spain
7Centro De Investigación Biomédica En Red De Epidemiología Y Salud Pública, Madrid, 28029, Spain
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Cedric Notredame
2Universitat Pompeu Fabra (UPF), Barcelona, 08003, Spain
4Comparative Bioinformatics, Bioinformatics, and Genomics Program, Barcelona Institute of Science and Technology, Centre for Genomic Regulation, Barcelona, 08003, Spain
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Mara Dierssen
1Cellular and Systems Neurobiology, Systems Biology Program, the Barcelona Institute of Science and Technology, Centre for Genomic Regulation (CRG), 08003, Barcelona, Spain
3Human Pharmacology and Clinical Neurosciences Research Group, Neurosciences Research Program, Hospital Del Mar Medical Research Institute (IMIM), Barcelona, 08003, Spain
8Centro De Investigación Biomédica En Red De Enfermedades Raras, Madrid, 28029, Spain
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Abstract

Intellectual disability in Down syndrome (DS) is accompanied by altered neuro-architecture, deficient synaptic plasticity, and excitation-inhibition imbalance in critical brain regions for learning and memory. Recently, we have demonstrated beneficial effects of a combined treatment with green tea extract containing (-)-epigallocatechin-3-gallate (EGCG) and cognitive stimulation in young adult DS individuals. Although we could reproduce the cognitive-enhancing effects in mouse models, the underlying mechanisms of these beneficial effects are unknown. Here, we explored the effects of a combined therapy with environmental enrichment (EE) and EGCG in the Ts65Dn mouse model of DS at young age. Our results show that combined EE-EGCG treatment improved corticohippocampal-dependent learning and memory. Cognitive improvements were accompanied by a rescue of cornu ammonis 1 (CA1) dendritic spine density and a normalization of the proportion of excitatory and inhibitory synaptic markers in CA1 and dentate gyrus.

  • (-)-epigallocatechin-3-gallate
  • Down syndrome
  • environmental enrichment
  • excitation-inhibition imbalance
  • neuroplasticity

Footnotes

  • Authors report no conflict of interest.

  • Authors Contribution: S.C.S. designed research, performed research, analyzed data, wrote the paper; J.E.-C., I.E., K.L., J.R.G. analyzed data; C.N. supervised the PCA analysis; M.D. provided financial support, designed research, wrote the paper.

  • This research was supported by DIUE of Generalitat de Catalunya (Grups consolidats SGR 2014/1125); Fondation Jérôme Lejeune (Paris, France); Spanish Ministry of Economy and Finance (MINECO) grants SAF2013-49129-C2-1-R, BFU2011-28575, and MTM2015-64465-C2-1-R CDTI (“Smartfoods”); the CIBER of Rare Diseases (ISCIII initiative); and EU-Era Net Neuron PCIN-2013-060. The CRG has received support as a Severo Ochoa Center of Excellence SEV- 2012-O208. S.C.-S. received a FPI doctoral Fellowship from the MINECO (SAF2010-16427).

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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Combined Treatment With Environmental Enrichment and (-)-Epigallocatechin-3-Gallate Ameliorates Learning Deficits and Hippocampal Alterations in a Mouse Model of Down Syndrome
Silvina Catuara-Solarz, Jose Espinosa-Carrasco, Ionas Erb, Klaus Langohr, Juan Ramon Gonzalez, Cedric Notredame, Mara Dierssen
eNeuro 19 October 2016, 3 (5) ENEURO.0103-16.2016; DOI: 10.1523/ENEURO.0103-16.2016

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Combined Treatment With Environmental Enrichment and (-)-Epigallocatechin-3-Gallate Ameliorates Learning Deficits and Hippocampal Alterations in a Mouse Model of Down Syndrome
Silvina Catuara-Solarz, Jose Espinosa-Carrasco, Ionas Erb, Klaus Langohr, Juan Ramon Gonzalez, Cedric Notredame, Mara Dierssen
eNeuro 19 October 2016, 3 (5) ENEURO.0103-16.2016; DOI: 10.1523/ENEURO.0103-16.2016
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Keywords

  • (-)-epigallocatechin-3-gallate
  • down Syndrome
  • environmental enrichment
  • Excitation-Inhibition Imbalance
  • neuroplasticity

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