Expression of fragile X mental retardation protein in neurons and glia of the developing and adult mouse brain
Expression of fragile X mental retardation protein in neurons and glia of the developing and adult mouse brain
复制标题
DOI：
10.1016/j.brainres.2014.11.023
复制
发表时间：
2015-01-30
期刊：
影响因子：
2.9
通讯作者：
Hampson, David R.
中科院分区：
文献类型：
--
作者：
Gholizadeh, Shervin;Halder, Sebok Kuvnar;Hampson, David R.
脆性 X 综合征是智力低下和自闭症最常见的遗传形式。它是由脆性X智力低下蛋白（FMRP）表达减少或消除引起的。由于脆性 X 综合征是一种神经发育障碍，因此完整记录发育中 CNS 中的细胞类型表达非常重要，以便更好地了解 FMRP 的分子功能以及该综合征的发病机制。我们使用双标记免疫细胞化学和神经元 (NeuN)、星形胶质细胞 (s100 beta)、小胶质细胞 (Iba-1) 和少突胶质细胞前体细胞 (NG2) 的细胞类型标记物研究了大脑中 FMRP 的表达。在野生型 C57/BL6 小鼠出生后第 0、10、20 天和成年时对海马、纹状体、扣带皮层、压后皮层、胼胝体和小脑进行了评估。我们的结果表明，FMRP 在所有时间的神经元和所研究的大脑区域中普遍表达，但胼胝体除外，其中 FMRP 主要存在于所有年龄段的星形胶质细胞中。在出生后第 0 天和第 10 天检测到 Iba-1 和 NG2 阳性细胞中的 FMRP 表达，并在出生后第 20 天和成年小鼠中逐渐降至非常低或不可检测的水平。我们的结果表明，除了在未成熟和成熟大脑的神经元中持续广泛表达外，FMRP 还存在于大脑成熟早期和中期的星形胶质细胞、少突胶质细胞前体细胞和小胶质细胞中。在大脑发育的这些关键阶段，神经胶质细胞中 FMRP 的显着表达表明对正常大脑功能有重要贡献，如果没有 FMRP，则对脆弱的 X 表型有重要贡献。 (C) 2014 Elsevier B.V. 保留所有权利。
Fragile X syndrome is the most common inherited form of mental retardation and autism. It is caused by a reduction or elimination of the expression of fragile X mental retardation protein (FMRP). Because fragile X syndrome is a neurodevelopmental disorder, it is important to fully document the cell type expression in the developing CNS to provide a better understanding of the molecular function of FMRP, and the pathogenesis of the syndrome. We investigated FMRP expression in the brain using double-labeling immunocytochemistry and cell type markers for neurons (NeuN), astrocytes (s100 beta), microglia (Iba-1), and oligodendrocyte precursor cells (NG2). The hippocampus, striatum, cingulate cortex, retrosplenial cortex, corpus callosum and cerebellum were assessed in wild-type C57/BL6 mice at postnatal days 0, 10, 20, and adult Our results demonstrate that FMRP is ubiquitously expressed in neurons at all times and brain regions studied, except for corpus callosum where FMRP was predominantly present in astrocytes at all ages. FMRP expression in Iba-1 and NG2-positive cells was detected at postnatal day 0 and 10 and gradually decreased to very low or undetectable levels in postnatal day 20 and adult mice. Our results reveal that in addition to continuous and extensive expression in neurons in the immature and mature brain, FMRP is also present in astrocytes, oligodendrocyte precursor cells, and microglia during the early and mid-postnatal developmental stages of brain maturation. Prominent expression of FMRP in glia during these crucial stages of brain development suggests an important contribution to normal brain function, and in its absence, to the fragile X phenotype. (C) 2014 Elsevier B.V. All rights reserved.