Upregulation in astrocytic connexin 43 gap junction levels may exacerbate generalized seizures in mesial temporal lobe epilepsy

Upregulation in astrocytic connexin 43 gap junction levels may exacerbate generalized seizures in mesial temporal lobe epilepsy
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DOI:
10.1016/s0006-8993(01)03289-9
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发表时间:
2002-03-01
期刊:
影响因子:
2.9
通讯作者:
Nicholson, LFB
Nicholson, LFB
中科院分区:
医学3区
文献类型:
--
作者:
Fonseca, CG;Green, CR;Nicholson, LFB

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脑损伤后,在神经退行性变的过程中,发生反应性星形胶质细胞增殖。这伴随着神经肽、细胞因子、生长因子和胶质细胞酸性蛋白(GFAP)(反应性星形胶质细胞的细胞特异性标志物)的合成增加。星形胶质细胞广泛耦合的间隙连接的Cx43连接蛋白亚型。一些研究表明,在严重创伤中,星形胶质细胞之间的耦合可能会增加受损区域的扩散。在这项研究中,我们问星形胶质细胞增多症,这是其他神经退行性疾病的一个特点,是否也发生在内侧颞叶癫痫(MTLE),它是否伴随着增加星形胶质细胞通信通过上调Cx43间隙连接通道蛋白。为了研究星形胶质细胞的反应和Cx43蛋白的表达模式,进行双重免疫组织化学标记研究,使用抗GFAP和Cx43的抗体应用于从MTLE患者切除的人海马组织。和正常人对照海马组织。免疫荧光标记的星形胶质细胞和Cx43进行了检查,使用共聚焦激光扫描显微镜。获得的图像进行定量分析和重建使用三维体绘制。这项研究的结果已经确定,不仅是星形胶质细胞比以前提出的更大的MTLE影响的组织,但它是伴随着一个非常显着的增加星形胶质细胞Cx43蛋白水平。我们推测,这一令人惊讶的大上调Cx43可能会加剧全身癫痫发作的进展MTLE。(C)2002 Elsevier Science B.V.保留所有权利。
Following brain injury, and during the process of neurodegeneration, a reactive astrocytic proliferation occurs. This is accompanied by an increase in the synthesis of neuropeptides, cytokines, growth factors and glial fibrillary acidic protein (GFAP), a cell-specific marker for reactive astrocytes. Astrocytes are extensively coupled by gap junctions of the Cx43 connexin subtype. Several studies have shown that in severe trauma, coupling between astrocytes may add to the spread of the damaged area. In this study we ask whether the astrocytosis which is a feature of other neurodegenerative diseases also occurs in mesial temporal lobe epilepsy (MTLE) and whether it is accompanied by an increase in astrocytic communication through an upregulation of Cx43 gap junction channel proteins. In order to examine the astrocytic response and the expression pattern of Cx43 protein, double immunohistochemical labeling studies were undertaken using antibodies against GFAP and Cx43 applied to human hippocampal tissue resected from patients with MTLE. and to normal human control hippocampal tissue. Immunofluorescent labeling of astrocytes and Cx43 was examined using confocal laser scanning microscopy. The images obtained were quantitatively analysed and reconstructed using three-dimensional volume rendering. The results of this study have established that not only is astrocytosis greater in MTLE-affected tissues than previously suggested, but it is accompanied by a highly significant increase in astrocytic Cx43 protein levels. We hypothesize that this surprisingly large upregulation in Cx43 may exacerbate generalized seizures in the progression of MTLE. (C) 2002 Elsevier Science B.V. All rights reserved.