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

- Enriched Ts65Dn mothers display increased levels of maternal care.
- Environmental enrichment from birth normalizes cognitive performance in Ts65Dn mice.
- Ts65Dn mice enriched from birth display a rescue of hippocampal LTP.
- Environmental enrichment from birth normalizes visual acuity maturation in Ts65Dn mice.
- Early enrichment normalizes v-GAT and BDNF in Ts65Dn mice.

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.