Enriched environment promotes behavioral and morphological recovery in a mouse model for the fragile X syndrome.
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.
Restivo
Leonardo
L
Laboratory of Psychobiology, Consiglio Nazionale delle Ricerche Institute of Neuroscience, 00179 Rome, Italy.
Ferrari
Francesca
F
Passino
Enrica
E
Sgobio
Carmelo
C
Bock
Jörg
J
Oostra
Ben A
BA
Bagni
Claudia
C
Ammassari-Teule
Martine
M
D000818:Animals; D001526:Behavioral Symptoms / Q000473:pathology*; D015153:Blotting, Western; D003712:Dendrites / Q000473:pathology*; D004780:Environment, Controlled; D005106:Exploratory Behavior / Q000502:physiology; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000473:pathology / Q000628:therapy*; D006185:Habituation, Psychophysiologic / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018091:Receptors, AMPA / Q000378:metabolism; D014793:Visual Cortex / Q000473:pathology*
D051860:Fragile X Messenger Ribonucleoprotein 1; D018091:Receptors, AMPA; C497684:Fmr1 protein, mouse