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

Leonardo Restivo, Francesca Ferrari, Enrica Passino, Carmelo Sgobio, Jörg Bock, Ben A. Oostra, Claudia Bagni, Martine Ammassari-Teule

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)11557-11562
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number32
DOIs
Publication statusPublished - Aug 9 2005

Keywords

  • AMPA receptor
  • Dendritic spines
  • FMR1 gene
  • Fragile X mental retardation protein
  • Mental retardation

ASJC Scopus subject areas

  • Genetics
  • General

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