GFAP isoforms in adult mouse brain with a focus on neurogenic astrocytes and reactive astrogliosis in mouse models of Alzheimer disease.
GFAP isoforms in adult mouse brain with a focus on neurogenic astrocytes and reactive astrogliosis in mouse models of Alzheimer disease.
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DOI：
10.1371/journal.pone.0042823
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hol EM
中科院分区：
文献类型：
--
作者：
Kamphuis W;Mamber C;Moeton M;Kooijman L;Sluijs JA;Jansen AH;Verveer M;de Groot LR;Smith VD;Rangarajan S;Rodríguez JJ;Orre M;Hol EM
胶质细胞酸性蛋白（GFAP）是星形胶质细胞的主要中间丝（IF）。GFAP剪接异构体在人脑中显示差异表达模式。GFAPδ优先由脑室下区（SVZ）中的神经源性星形胶质细胞表达，而GFAP+1在整个脑中的星形胶质细胞亚群中发现。此外，这些异构体在癫痫、阿尔茨海默病和胶质瘤患者的人脑材料中的表达也有报道。在这里，我们第一次提出了一个全面的研究GFAP亚型表达在野生型和阿尔茨海默病（AD）小鼠模型。在野生型小鼠的皮质、小脑和纹状体中，检测到Gfap-α、Gfap-β、Gfap-γ、Gfap-δ、Gfap-κ和新鉴定的同种型Gfap-κ的转录物。它们的相对表达水平在研究的所有区域中相似。GFAPα广泛表达，而GFAPδ在SVZ、吻侧迁移流（RMS）、颗粒下带（SGZ）的神经源性星形胶质细胞和软膜下星形胶质细胞中分布显著。与人SVZ相反，我们不能在小鼠SVZ的增殖细胞中建立明确的GFAPδ定位。在APPswePS 1dE 9和3xTgAD小鼠中，斑块相关反应性星形胶质细胞所有可检测的GFAP亚型的转录水平增加，新的GFAP亚型GFap-Δ Ex 7的水平降低。AD小鼠反应性星形胶质细胞显示GFAPα和GFAPδ免疫标记增强，波形蛋白和巢蛋白表达较少，但无GFAPκ或GFAP+1染色。总之，GFAPδ蛋白存在于SVZ、RMS和SGZ的神经源性星形胶质细胞中，但也存在于神经源性小生境之外。此外，差异GFAP亚型表达与衰老或反应性神经胶质增生无关。这一证据表明，GFAP亚型的差异调节并不参与反应性胶质增生或小鼠大脑神经发生中IF网络的重组。
Glial fibrillary acidic protein (GFAP) is the main astrocytic intermediate filament (IF). GFAP splice isoforms show differential expression patterns in the human brain. GFAPδ is preferentially expressed by neurogenic astrocytes in the subventricular zone (SVZ), whereas GFAP+1 is found in a subset of astrocytes throughout the brain. In addition, the expression of these isoforms in human brain material of epilepsy, Alzheimer and glioma patients has been reported. Here, for the first time, we present a comprehensive study of GFAP isoform expression in both wild-type and Alzheimer Disease (AD) mouse models. In cortex, cerebellum, and striatum of wild-type mice, transcripts for Gfap-α, Gfap-β, Gfap-γ, Gfap-δ, Gfap-κ, and a newly identified isoform Gfap-ζ, were detected. Their relative expression levels were similar in all regions studied. GFAPα showed a widespread expression whilst GFAPδ distribution was prominent in the SVZ, rostral migratory stream (RMS), neurogenic astrocytes of the subgranular zone (SGZ), and subpial astrocytes. In contrast to the human SVZ, we could not establish an unambiguous GFAPδ localization in proliferating cells of the mouse SVZ. In APPswePS1dE9 and 3xTgAD mice, plaque-associated reactive astrocytes had increased transcript levels of all detectable GFAP isoforms and low levels of a new GFAP isoform, Gfap-ΔEx7. Reactive astrocytes in AD mice showed enhanced GFAPα and GFAPδ immunolabeling, less frequently increased vimentin and nestin, but no GFAPκ or GFAP+1 staining. In conclusion, GFAPδ protein is present in SVZ, RMS, and neurogenic astrocytes of the SGZ, but also outside neurogenic niches. Furthermore, differential GFAP isoform expression is not linked with aging or reactive gliosis. This evidence points to the conclusion that differential regulation of GFAP isoforms is not involved in the reorganization of the IF network in reactive gliosis or in neurogenesis in the mouse brain.
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DOI：
10.1126/science.1169096
发表时间：
2009-02-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kuchibhotla KV;Lattarulo CR;Hyman BT;Bacskai BJ
通讯作者：
Bacskai BJ
影响因子：
4.2
作者：
FEINSTEIN, DL;WEINMASTER, GA;MILNER, RJ
通讯作者：
MILNER, RJ
影响因子：
6.2
作者：
Kamphuis, Willem;Orre, Marie;Hol, Elly M.
通讯作者：
Hol, Elly M.
影响因子：
16
作者：
Bandyopadhyay U;Sridhar S;Kaushik S;Kiffin R;Cuervo AM
通讯作者：
Cuervo AM
影响因子：
18.2
作者：
Halassa MM;Haydon PG
通讯作者：
Haydon PG