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

eNeuro. 2016 Nov 8;3(5):ENEURO.0103-16.2016. doi: 10.1523/ENEURO.0103-16.2016. eCollection 2016 Sep-Oct.

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.

Keywords: (-)-epigallocatechin-3-gallate; Down syndrome; environmental enrichment; excitation-inhibition imbalance; neuroplasticity.

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / metabolism
  • CA1 Region, Hippocampal / pathology*
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Dendritic Spines / drug effects
  • Dendritic Spines / metabolism
  • Dendritic Spines / pathology
  • Disease Models, Animal
  • Down Syndrome / metabolism
  • Down Syndrome / pathology
  • Down Syndrome / therapy*
  • Housing, Animal*
  • Learning* / drug effects
  • Mice, Transgenic
  • Nootropic Agents / pharmacology*
  • Plant Extracts / pharmacology
  • Random Allocation
  • Recognition, Psychology / drug effects
  • Synapses / drug effects
  • Synapses / metabolism
  • Synapses / pathology
  • Tea
  • Vesicular Glutamate Transport Protein 1 / metabolism
  • Vesicular Inhibitory Amino Acid Transport Proteins / metabolism

Substances

  • Nootropic Agents
  • Plant Extracts
  • Slc17a7 protein, mouse
  • Tea
  • Vesicular Glutamate Transport Protein 1
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • Viaat protein, mouse
  • Catechin
  • epigallocatechin gallate