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 - Tập 102 Số 32 - Trang 11557-11562 - 2005
Leonardo Restivo1, Francesca Ferrari1, Enrica Passino1, Carmelo Sgobio1, Jörg Bock1, Ben A. Oostra1, Claudia Bagni1, Martine Ammassari‐Teule1
1Laboratory of Psychobiology, Consiglio Nazionale delle Ricerche Institute of Neuroscience, 00179 Rome, Italy; Department of Experimental Neurology, Fondazione Santa Lucia, Istituto Ricovero e Cura a Carattere Scientifico, 00179 Rome, Italy; Institute of Biology, Department of Zoology and Developmental Neurobiology, Otto-von-Guericke University, 39118 Magdeburg, Germany; Department of Clinical Genetics, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands; and Department of Biology, University...

Tóm tắt

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

Tập 102 Số 32

11557-11562

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