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

By Weixiang Guo, A. Allan, Ruiting Zong, Li Zhang, Eric B. Johnson, Eric G Schaller, Adeline C Murthy, Samantha L. Goggin, A. Eisch, B. Oostra and 3 more. 2011

229 citations recorded by the source corpus.

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.

Subfields: Developmental Neuroscience, Genetics, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Developmental Neuroscience

1. Hongjun Song
2. Guo-li Ming
3. Fred H. Gage
4. James Bradley Aimone
5. Chunmei Zhao
6. Wei Deng
7. R. Hen
8. Sebastian Jessberger

In Genetics

1. Guo-li Ming
2. Hongjun Song
3. German Ignacio Parisi
4. Fred H. Gage

In Molecular Biology

1. Hongjun Song
2. Guo-li Ming
3. Fred H. Gage
4. German Ignacio Parisi

Citations in the corpus

• Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions (2011, background): “…promote BDNF and FGF1 expression in mature dentate granule cells in response to neuronal activation and deletion of Gadd45b reduces activity-induced proliferation of neural precursors and dendritic growth of newborn neurons in the adult hippocampus (Guo et al., 2011a; Ma et al., 2009).”
• Adult hippocampal neurogenesis, Rho kinase inhibition and enhancement of neuronal survival. (2013, background): “When examining role of Fmrp in neurogenesis, Guo and colleagues specifically note the lack of change in the object recognition task as further evidence to the role Fmrp has in hippocampus-dependent learning (Guo et al., 2011).”