TY - JOUR
T1 - Early environmental therapy rescues brain development in a mouse model of Down syndrome
AU - Begenisic, Tatjana
AU - Sansevero, Gabriele
AU - Baroncelli, Laura
AU - Cioni, Giovanni
AU - Sale, Alessandro
PY - 2015/10/1
Y1 - 2015/10/1
N2 - 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.
AB - 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.
KW - BDNF
KW - Down syndrome
KW - Environmental enrichment
KW - GABA
KW - Hippocampal plasticity
KW - Maternal care
KW - Ts65Dn mice
KW - Visual system
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U2 - 10.1016/j.nbd.2015.07.014
DO - 10.1016/j.nbd.2015.07.014
M3 - Article
C2 - 26244989
AN - SCOPUS:84939448495
VL - 82
SP - 409
EP - 419
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
ER -