Waisman Center and Department of Neuroscience, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53705, USA.
Hum Mol Genet. 2012 Feb 1;21(3):681-91. doi: 10.1093/hmg/ddr501. Epub 2011 Nov 2.
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 3β (GSK3β), we investigated the effects of a GSK3β inhibitor, SB216763, on Fmr1 knockout mice (Fmr1 KO). We found that the inhibition of GSK3β could reverse the hippocampus-dependent learning deficits and rescue adult hippocampal neurogenesis at multiple stages in Fmr1 KO mice. Our results point to GSK3β inhibition as a potential treatment for the learning deficits seen in FXS.
脆性 X 综合征（FXS）是一种常见的遗传性智力障碍，伴有学习缺陷，是由于脆性 X 智力低下蛋白（FMRP）的缺失引起的。尽管进行了广泛的研究，但 FXS 的治疗选择仍然有限。由于已知 FMRP 在成年海马神经发生和海马依赖的学习中发挥重要作用，并且 FMRP 通过翻译调节糖原合酶激酶 3β（GSK3β）来调节成年神经干细胞命运，我们研究了 GSK3β 抑制剂 SB216763 对 Fmr1 敲除小鼠（Fmr1 KO）的影响。我们发现，抑制 GSK3β 可以逆转 Fmr1 KO 小鼠的海马依赖学习缺陷，并在多个阶段挽救成年海马神经发生。我们的结果表明，抑制 GSK3β 可能是治疗 FXS 中所见学习缺陷的一种潜在方法。
