Enriched environment promotes behavioral and morphological recovery in a mouse model for the fragile X syndrome
Proceedings of the National Academy of Sciences of the United States of America , Volume 102 - Issue 32 p. 11557- 11562
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.
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|Proceedings of the National Academy of Sciences of the United States of America|
|Organisation||Department of Clinical Genetics|
Restivo, L, Ferrari, F, Passino, E, Sgobio, C, de Bock, G.H, Oostra, B.A, … Ammassari-Teule, M. (2005). Enriched environment promotes behavioral and morphological recovery in a mouse model for the fragile X syndrome. Proceedings of the National Academy of Sciences of the United States of America, 102(32), 11557–11562. doi:10.1073/pnas.0504984102