S. Pietropaolo & W.Crusio inNeuropsychopharmacology

Two mothers are better than one: early social enrichment rescues the neurobehavioural deficits of a mouse model of Fragile X syndrome

Early Social Enrichment Rescues Adult Behavioral and Brain Abnormalities in a Mouse Model of Fragile X Syndrome.
Oddi D, Subashi E, Middei S, Bellocchio L, Lemaire-Mayo V, Guzmán M, Crusio WE, D’Amato FR, Pietropaolo S. Neuropsychopharmacology. 2014 Oct 28. doi: 10.1038/npp.2014.291

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. In collaboration with Dr. Francesca D’amato at the CNR of Rome 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 major 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 non-lactating female.

Enrichment rescued the behavioral FXS-like deficits displayed in adulthood by Fmr1-KO mice, i.e., 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 versus 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 non-pharmacological interventions for the treatment of this and perhaps other neurodevelopmental diseases.