Reduced cortical synaptic plasticity and GluR1 expression associated with fragile X mental retardation protein deficiency
Reduced cortical synaptic plasticity and GluR1 expression associated with fragile X mental retardation protein deficiency
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DOI：
10.1006/mcne.2001.1085
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发表时间：
2002-02-01
影响因子：
3.5
通讯作者：
Carlen, PL
中科院分区：
文献类型：
--
作者：
Li, JX;Pelletier, MR;Carlen, PL
脆性X智力低下蛋白（FMRP）的表达缺乏，由于FMR 1基因的沉默，导致脆性X综合征。尽管FMRP以前被鉴定为RNA结合蛋白，但对其功能或脆性X综合征的潜在机制知之甚少。在这里，我们报告说，α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体亚基，GluR 1，减少皮质突触，但不是在海马或小脑，FMR 1基因敲除小鼠。长时程增强（LTP）减少也发现在皮层，但不是在海马。另一种RNA结合蛋白，FXR; N-甲基-D-天冬氨酸受体亚基，NR 2;和其他学习相关蛋白，包括c-fos，突触蛋白，髓鞘蛋白脂质蛋白和cAMP反应元件结合蛋白在FMR 1基因敲除小鼠和野生型小鼠之间没有差异。这些结果表明，皮质GluR 1表达和LTP与FMRP缺乏可能有助于脆性X表型。
Lack of expression of the fragile X mental retardation protein (FMRP), due to silencing of the FMR1 gene, causes the Fragile X syndrome. Although FMRP was characterized previously to be an RNA binding protein, little is known about its function or the mechanisms underlying the Fragile X syndrome. Here we report that the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit, GluR1, was decreased in the cortical synapses, but not in the hippocampus or cerebellum, of FMR1 gene knockout mice. Reduced long-term potentiation (LTP) was also found in the cortex but not in the hippocampus. Another RNA binding protein, FXR; the N-methyl-D-aspartate receptor subunit, NR2; and other learning-related proteins including c-fos, synapsin, myelin proteolipid protein, and cAMP response element binding protein were not different between FMR1 gene knockout and wild-type mice. These findings suggest that the depressed cortical GluR1 expression and LTP associated with FMRP deficiency could contribute to the Fragile X phenotype.