Early Social Enrichment Rescues Adult Behavioral and Brain Abnormalities in a Mouse Model of Fragile X Syndrome
Neuropsychopharmacol. 2014-10-28; 40(5): 1113-1122
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Oddi D(1), Subashi E(2), Middei S(1), Bellocchio L(3), Lemaire-Mayo V(2), Guzmán M(3), Crusio WE(2), D’Amato FR(1), Pietropaolo S(2).
(1)1] CNR, Cell Biology and Neurobiology Institute, Rome, Italy  IRCCS, Santa Lucia Foundation, Rome, Italy.
(2)1] Université Bordeaux, INCIA, Talence, France  CNRS, INCIA, UMR5287,
(3)Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University and CIBERNED, Madrid, Spain.
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