title: Early environmental therapy rescues brain development in a mouse model of Down syndrome.
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.
authors.affiliation: Neuroscience Institute CNR, Pisa I-56100, Italy.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Begenisic
authors.affiliation: Neuroscience Institute CNR, Pisa I-56100, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Sansevero
authors.affiliation: Neuroscience Institute CNR, Pisa I-56100, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Baroncelli
authors.affiliation: Department of Developmental Neuroscience, IRCCS Stella Maris, University of Pisa, Calambrone, I-56100 Pisa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cioni
authors.affiliation: Neuroscience Institute CNR, Pisa I-56100, Italy. Electronic address: sale@in.cnr.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sale
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000503:physiopathology* / Q000523:psychology / Q000628:therapy*; D004777:Environment; D005074:Evoked Potentials, Visual; D005260:Female; D006624:Hippocampus / Q000254:growth & development / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D008425:Maternal Behavior; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D021641:Recognition, Psychology / Q000502:physiology; D046509:Tissue Culture Techniques; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism; D014792:Visual Acuity; D014795:Visual Pathways / Q000254:growth & development / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; D005680:gamma-Aminobutyric Acid
keywords: BDNF; Down syndrome; Environmental enrichment; GABA; Hippocampal plasticity; Maternal care; Ts65Dn mice; Visual system