Enriched environment promotes behavioral and morphological recovery in a mouse model for the fragile X syndrome

L Restivo, F Ferrari, E Passino… - Proceedings of the …, 2005 - National Acad Sciences
L Restivo, F Ferrari, E Passino, C Sgobio, J Bock, BA Oostra, C Bagni, M Ammassari-Teule
Proceedings of the National Academy of Sciences, 2005National Acad Sciences
Fragile X syndrome, the most frequent form of hereditary mental retardation, is due to a
mutation of the fragile X mental retardation 1 (FMR1) gene on the X chromosome. Like
fragile X patients, FMR1-knockout (FMR1-KO) mice lack the normal fragile X mental
retardation protein (FMRP) and show both cognitive alterations and an immature neuronal
morphology. We reared FMR1-KO mice in a C57BL/6 background in enriched
environmental conditions to examine the possibility that experience-dependent stimulation …
Fragile X syndrome, the most frequent form of hereditary mental retardation, is due to a mutation of the fragile X mental retardation 1 (FMR1) gene on the X chromosome. Like fragile X patients, FMR1-knockout (FMR1-KO) mice lack the normal fragile X mental retardation protein (FMRP) and show both cognitive alterations and an immature neuronal morphology. We reared FMR1-KO mice in a C57BL/6 background in enriched environmental conditions to examine the possibility that experience-dependent stimulation alleviates their behavioral and neuronal abnormalities. FMR1-KO mice kept in standard cages were hyperactive, displayed an altered pattern of open field exploration, and did not show habituation. Quantitative morphological analyses revealed a reduction in basal dendrite length and branching together with more immature-appearing spines along apical dendrites of layer five pyramidal neurons in the visual cortex. Enrichment largely rescued these behavioral and neuronal abnormalities while increasing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor subunit 1 (GluR1) levels in both genotypes. Enrichment did not, however, affect FMRP levels in the WT mice. These data suggest that FMRP-independent pathways activating glutamatergic signaling are preserved in FMR1-KO mice and that they can be elicited by environmental stimulation.
National Acad Sciences