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.
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| http://dx.doi.org/10.1038/nm.2336 | DOI Listing |
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Article Synopsis
- FMRP, a protein regulated by the FMR1 gene, plays a critical role in modulating synaptic plasticity and local translation in the nervous system, and mutations in this gene can lead to Fragile X Syndrome, which is linked to sensory processing issues.
- Research shows that FMRP may influence pain perception by affecting neuron excitability and the way sensory signals are processed, particularly in the dorsal root ganglion and spinal cord.
- Immunostaining revealed high FMRP expression in specific spinal neuron subsets, with notable links to receptors associated with pain response, especially highlighting differences in how this protein interacts with pain signals in males and females.
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