In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 102, No. 32 ( 2005-08-09), p. 11557-11562
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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0504984102
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2005
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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