Early environmental therapy rescues brain development in a mouse model of Down syndrome

Tatjana Begenisic, Gabriele Sansevero, Laura Baroncelli, Giovanni Cioni, Alessandro Sale

Research output: Contribution to journalArticlepeer-review

Abstract

Down syndrome (DS), the most common genetic disorder associated with intellectual disabilities, is an untreatable condition characterized by a number of developmental defects and permanent deficits in the adulthood. Ts65Dn mice, the major animal model for DS, display severe cognitive and synaptic plasticity defects closely resembling the human phenotype. Here, we employed a multidisciplinary approach to investigate, for the first time in developing Ts65Dn mice, the effects elicited by early environmental enrichment (EE) on brain maturation and function. We report that exposure to EE resulted in a robust increase in maternal care levels displayed by Ts65Dn mothers and led to a normalization of declarative memory abilities and hippocampal plasticity in trisomic offspring. The positive effects of EE on Ts65Dn phenotype were not limited to the cognitive domain, but also included a rescue of visual system maturation. The beneficial EE effects were accompanied by increased BDNF and correction of over-expression of the GABA vesicular transporter vGAT. These findings highlight the beneficial impact of early environmental stimuli and their potential for application in the treatment of major functional deficits in children with DS.

Original languageEnglish
Pages (from-to)409-419
Number of pages11
JournalNeurobiology of Disease
Volume82
DOIs
Publication statusPublished - Oct 1 2015

Keywords

  • BDNF
  • Down syndrome
  • Environmental enrichment
  • GABA
  • Hippocampal plasticity
  • Maternal care
  • Ts65Dn mice
  • Visual system

ASJC Scopus subject areas

  • Neurology

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