title: Combined Treatment With Environmental Enrichment and (-)-Epigallocatechin-3-Gallate Ameliorates Learning Deficits and Hippocampal Alterations in a Mouse Model of Down Syndrome.
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.
authors.affiliation: Cellular and Systems Neurobiology, Systems Biology Program, the Barcelona Institute of Science and Technology, Centre for Genomic Regulation (CRG), 08003, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, 08003, Spain; Human Pharmacology and Clinical Neurosciences Research Group, Neurosciences Research Program, Hospital Del Mar Medical Research Institute (IMIM), Barcelona, 08003, Spain.
authors.forename: Silvina
authors.identifier: 0000-0002-1514-0431
authors.initials: S
authors.lastname: Catuara-Solarz
authors.affiliation: Cellular and Systems Neurobiology, Systems Biology Program, the Barcelona Institute of Science and Technology, Centre for Genomic Regulation (CRG), 08003, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, 08003, Spain; Comparative Bioinformatics, Bioinformatics, and Genomics Program, Barcelona Institute of Science and Technology, Centre for Genomic Regulation, Barcelona, 08003, Spain.
authors.forename: Jose
authors.identifier: 0000-0002-1541-042X
authors.initials: J
authors.lastname: Espinosa-Carrasco
authors.affiliation: Universitat Pompeu Fabra (UPF), Barcelona, 08003, Spain; Comparative Bioinformatics, Bioinformatics, and Genomics Program, Barcelona Institute of Science and Technology, Centre for Genomic Regulation, Barcelona, 08003, Spain.
authors.forename: Ionas
authors.identifier: 0000-0002-2331-9714
authors.initials: I
authors.lastname: Erb
authors.affiliation: Human Pharmacology and Clinical Neurosciences Research Group, Neurosciences Research Program, Hospital Del Mar Medical Research Institute (IMIM), Barcelona, 08003, Spain; Department of Statistics and Operations Research, Universitat Politècnica De Catalunya/BarcelonaTech, Barcelona, 08034, Spain.
authors.forename: Klaus
authors.identifier: 0000-0001-7075-9192
authors.initials: K
authors.lastname: Langohr
authors.affiliation: Centre for Research in Environmental Epidemiology, Barcelona, 08003, Spain; Centro De Investigación Biomédica En Red De Epidemiología Y Salud Pública, Madrid, 28029, Spain.
authors.forename: Juan Ramon
authors.initials: JR
authors.lastname: Gonzalez
authors.affiliation: Universitat Pompeu Fabra (UPF), Barcelona, 08003, Spain; Comparative Bioinformatics, Bioinformatics, and Genomics Program, Barcelona Institute of Science and Technology, Centre for Genomic Regulation, Barcelona, 08003, Spain.
authors.forename: Cedric
authors.initials: C
authors.lastname: Notredame
authors.affiliation: Cellular and Systems Neurobiology, Systems Biology Program, the Barcelona Institute of Science and Technology, Centre for Genomic Regulation (CRG), 08003, Barcelona, Spain; Human Pharmacology and Clinical Neurosciences Research Group, Neurosciences Research Program, Hospital Del Mar Medical Research Institute (IMIM), Barcelona, 08003, Spain; Centro De Investigación Biomédica En Red De Enfermedades Raras, Madrid, 28029, Spain.
authors.forename: Mara
authors.identifier: 0000-0003-0853-6865
authors.initials: M
authors.lastname: Dierssen
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006799:Housing, Animal; D007858:Learning / Q000187:drug effects; D008822:Mice, Transgenic; D018697:Nootropic Agents / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D011897:Random Allocation; D021641:Recognition, Psychology / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013662:Tea; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism
chemical_list: D018697:Nootropic Agents; D010936:Plant Extracts; C493465:Slc17a7 protein, mouse; D013662:Tea; D050598:Vesicular Glutamate Transport Protein 1; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; D002392:Catechin; C045651:epigallocatechin gallate
keywords: (-)-epigallocatechin-3-gallate; Down syndrome; environmental enrichment; excitation-inhibition imbalance; neuroplasticity