title: Early environmental enrichment moderates the behavioral and synaptic phenotype of MeCP2 null mice.
abstract: BACKGROUND
  Rett syndrome (RTT) is an X-linked progressive neurodevelopmental disorder characterized by a variety of symptoms including motor abnormalities, mental retardation, anxiety, and autism. Most of RTT cases are caused by mutations of MeCP2. In mice, impaired MeCP2 function results in synaptic deficits associated with motor, cognitive, and emotional alterations. Environmental enrichment (EE) is a rearing condition that enhances synapse formation and plasticity. Previous studies analyzing the effects of postweaning EE found limited effects on motor performance of male MeCP2 mutants. However, EE during early postnatal development produces powerful effects on neural development and plasticity. Thus, we tested whether early EE could ameliorate several phenotypes of male homozygous and female heterozygous MeCP2 mutants.
  
  
  METHODS
  We investigated the effects of early EE on motor coordination, structural and functional synaptic plasticity, and brain-derived neurotrophic factor expression in male MeCP2 null mice. Anxiety-related behavior and spatial learning was analyzed in heterozygous MeCP2 female mice.
  
  
  RESULTS
  In male mutants, EE modified excitatory and to a lesser extent inhibitory synaptic density in cerebellum and cortex, reversed the cortical long-term potentiation deficit and augmented cortical brain-derived neurotrophic factor levels. Environmental enrichment also ameliorated motor coordination and motor learning. In female heterozygous mice, a model closely mimicking some aspects of RTT symptoms, EE rescued memory deficits in the Morris water maze and decreased anxiety-related behavior.
  
  
  CONCLUSIONS
  Early EE dramatically improves several phenotypes of MeCP2 mutants. Thus, environmental factors should be taken into account when analyzing phenotypes of MeCP2 knockout mice, an accepted model of RTT. Early EE might be beneficial in RTT patients.
authors.affiliation: CNR, Neuroscience Institute Pisa, 56100 Pisa, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Lonetti
authors.forename: Andrea
authors.initials: A
authors.lastname: Angelucci
authors.forename: Laura
authors.initials: L
authors.lastname: Morando
authors.forename: Elena M
authors.initials: EM
authors.lastname: Boggio
authors.forename: Maurizio
authors.initials: M
authors.lastname: Giustetto
authors.forename: Tommaso
authors.initials: T
authors.lastname: Pizzorusso
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D003072:Cognition Disorders / Q000235:genetics / Q000503:physiopathology; D004195:Disease Models, Animal; D004777:Environment; D008297:Male; D018782:Maze Learning; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010641:Phenotype; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism; D013569:Synapses
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051783:Methyl-CpG-Binding Protein 2