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Nat Med. 2011 May;17(5):559-65. doi: 10.1038/nm.2336. Epub 2011 Apr 24.

Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning.

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1
Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.

Abstract

Deficiency in fragile X mental retardation protein (FMRP) results in fragile X syndrome (FXS), an inherited form of intellectual disability. Despite extensive research, it is unclear how FMRP deficiency contributes to the cognitive deficits in FXS. Fmrp-null mice show reduced adult hippocampal neurogenesis. As Fmrp is also enriched in mature neurons, we investigated the function of Fmrp expression in neural stem and progenitor cells (aNSCs) and its role in adult neurogenesis. Here we show that ablation of Fmrp in aNSCs by inducible gene recombination leads to reduced hippocampal neurogenesis in vitro and in vivo, as well as markedly impairing hippocampus-dependent learning in mice. Conversely, restoration of Fmrp expression specifically in aNSCs rescues these learning deficits in Fmrp-deficient mice. These data suggest that defective adult neurogenesis may contribute to the learning impairment seen in FXS, and these learning deficits can be rectified by delayed restoration of Fmrp specifically in aNSCs.

PMID:
21516088
PMCID:
PMC3140952
DOI:
10.1038/nm.2336
[Indexed for MEDLINE]
Free PMC Article

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