Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning.
Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning.
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脆性X智力低下蛋白(FMRP)缺陷会导致脆性X综合征(FXS)，这是一种遗传性智力残疾形式。尽管有广泛的研究，但FMRP缺陷如何导致FXS的认知缺陷尚不清楚。我们之前已经证明，FMRP缺失的小鼠表现出成年海马神经发生减少。由于FMRP也在成熟神经元中丰富，我们探讨了FMRP在神经干细胞和祖细胞(ANSCs)中表达的功能意义及其在成年神经发生中的作用。在这里，我们展示了通过可诱导的基因重组去除aNSCs中的FMRP导致体外和体内海马神经发生减少，以及显著损害小鼠的海马区依赖学习。相反，在aNSCs中恢复FMRP的表达可以挽救这些学习缺陷。这些数据表明，成人神经发生缺陷可能导致FXS中的学习障碍，这些学习障碍可以通过延迟恢复FMRP来纠正，特别是在aNSCs中。
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.
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DOI：
10.1634/stemcells.2008-0519
发表时间：
2008-12
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Barkho BZ;Munoz AE;Li X;Li L;Cunningham LA;Zhao X
通讯作者：
Zhao X
影响因子：
2.5
作者：
Brennan, F. X.;Albeck, D. S.;Paylor, R.
通讯作者：
Paylor, R.
影响因子：
25
作者：
Imayoshi, Itaru;Sakamoto, Masayuki;Kageyama, Ryoichiro
通讯作者：
Kageyama, Ryoichiro
影响因子：
3.5
作者：
Allan, Andrea M.;Liang, Xiaomin;Zhao, Xinyu
通讯作者：
Zhao, Xinyu
影响因子：
2
作者：
Harrell, AV;Allan, AM
通讯作者：
Allan, AM