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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