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

Deficiency in fragile X mental retardation protein (FMRP) results in fragile X syndrome (FXS), an inherited form of intellectual disability. Despite extensive research, how FMRP deficiency contributes to the cognitive deficits in FXS is unclear. We have previously shown that Fmrp-null mice exhibit reduced adult hippocampal neurogenesis. Since Fmrp is also enriched in mature neurons, we explored the functional significance of Fmrp expression in neural stem and progenitor cells (aNSCs) and its role in adult neurogenesis. Here we show ablation of Fmrp in aNSCs via inducible gene recombination leads to reduced hippocampal neurogenesis in vitro and in vivo, as well as significantly impaired hippocampus-dependent learning in mice. Conversely, restoration of Fmrp expression specifically in aNSCs rescues these learning deficits. 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

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc