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

Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11557-62. doi: 10.1073/pnas.0504984102. Epub 2005 Aug 2.

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 alpha-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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavioral Symptoms / pathology*
  • Blotting, Western
  • Dendrites / pathology*
  • Environment, Controlled*
  • Exploratory Behavior / physiology
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Syndrome / pathology
  • Fragile X Syndrome / therapy*
  • Habituation, Psychophysiologic / genetics
  • Habituation, Psychophysiologic / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, AMPA / metabolism
  • Visual Cortex / pathology*

Substances

  • Fmr1 protein, mouse
  • Receptors, AMPA
  • Fragile X Mental Retardation Protein
  • glutamate receptor ionotropic, AMPA 1