title: Early social enrichment rescues adult behavioral and brain abnormalities in a mouse model of fragile X syndrome.
abstract: Converging lines of evidence support the use of environmental stimulation to ameliorate the symptoms of a variety of neurodevelopmental disorders. Applying these interventions at very early ages is critical to achieve a marked reduction of the pathological phenotypes. Here we evaluated the impact of early social enrichment in Fmr1-KO mice, a genetic mouse model of fragile X syndrome (FXS), a major developmental disorder and the most frequent monogenic cause of autism. Enrichment was achieved by providing male KO pups and their WT littermates with enhanced social stimulation, housing them from birth until weaning with the mother and an additional nonlactating female. At adulthood they were tested for locomotor, social, and cognitive abilities; furthermore, dendritic alterations were assessed in the hippocampus and amygdala, two brain regions known to be involved in the control of the examined behaviors and affected by spine pathology in Fmr1-KOs. Enrichment rescued the behavioral FXS-like deficits displayed in adulthood by Fmr1-KO mice, that is, hyperactivity, reduced social interactions, and cognitive deficits. Early social enrichment also eliminated the abnormalities shown by adult KO mice in the morphology of hippocampal and amygdala dendritic spines, namely an enhanced density of immature vs mature types. Importantly, enrichment did not induce neurobehavioral changes in WT mice, thus supporting specific effects on FXS-like pathology. These findings show that early environmental stimulation has profound and long-term beneficial effects on the pathological FXS phenotype, thereby encouraging the use of nonpharmacological interventions for the treatment of this and perhaps other neurodevelopmental diseases.
authors.affiliation: 1] CNR, Cell Biology and Neurobiology Institute, Rome, Italy [2] IRCCS, Santa Lucia Foundation, Rome, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Oddi
authors.affiliation: 1] Université Bordeaux, INCIA, Talence, France [2] CNRS, INCIA, UMR5287, Talence, France.
authors.forename: Enejda
authors.initials: E
authors.lastname: Subashi
authors.affiliation: 1] CNR, Cell Biology and Neurobiology Institute, Rome, Italy [2] IRCCS, Santa Lucia Foundation, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Middei
authors.affiliation: Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University and CIBERNED, Madrid, Spain.
authors.forename: Luigi
authors.initials: L
authors.lastname: Bellocchio
authors.affiliation: 1] Université Bordeaux, INCIA, Talence, France [2] CNRS, INCIA, UMR5287, Talence, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Lemaire-Mayo
authors.affiliation: Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University and CIBERNED, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Guzmán
authors.affiliation: 1] Université Bordeaux, INCIA, Talence, France [2] CNRS, INCIA, UMR5287, Talence, France.
authors.forename: Wim E
authors.initials: WE
authors.lastname: Crusio
authors.affiliation: 1] CNR, Cell Biology and Neurobiology Institute, Rome, Italy [2] IRCCS, Santa Lucia Foundation, Rome, Italy.
authors.forename: Francesca R
authors.initials: FR
authors.lastname: D'Amato
authors.affiliation: 1] Université Bordeaux, INCIA, Talence, France [2] CNRS, INCIA, UMR5287, Talence, France.
authors.forename: Susanna
authors.initials: S
authors.lastname: Pietropaolo
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D003071:Cognition; D015331:Cohort Studies; D049229:Dendritic Spines / Q000473:pathology; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000473:pathology* / Q000523:psychology / Q000628:therapy*; D046352:Freezing Reaction, Cataleptic; D008124:Locomotion; D008297:Male; D008425:Maternal Behavior; D008426:Maternal Deprivation; D018345:Mice, Knockout; D012919:Social Behavior; D016896:Treatment Outcome; D014465:Ultrasonics; D014828:Vocalization, Animal
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497684:Fmr1 protein, mouse