Inhibition of GSK3β improves hippocampus-dependent learning and rescues neurogenesis in a mouse model of fragile X syndrome

Fragile X syndrome (FXS), a common inherited form of intellectual disability with learning deficits, results from a loss of fragile X mental retardation protein (FMRP). Despite extensive research, treatment options for FXS remain limited. Since FMRP is known to play an important role in adult hippocampal neurogenesis and hippocampus-dependent learning and FMRP regulates the adult neural stem cell fate through the translational regulation of glycogen synthase kinase 3b (GSK3b), we investigated the effects of a GSK3b inhibitor, SB216763, on Fmr1 knockout mice (Fmr1 KO). We found that the inhibition of GSK3b could reverse the hippocampus-dependent learning deficits and rescue adult hippocampal neurogenesis at multiple stages in Fmr1 KO mice. Our results point to GSK3b inhibition as a potential treatment for the learning deficits seen in FXS.