CELL TYPE-SPECIFIC LOCALIZATION OF OPTINEURIN IN THE STRIATAL NEURONS OF MICE: IMPLICATIONS FOR NEURONAL VULNERABILITY IN HUNTINGTON'S DISEASE
CELL TYPE-SPECIFIC LOCALIZATION OF OPTINEURIN IN THE STRIATAL NEURONS OF MICE: IMPLICATIONS FOR NEURONAL VULNERABILITY IN HUNTINGTON'S DISEASE
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DOI：
10.1016/j.neuroscience.2011.11.059
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发表时间：
2012-01-27
期刊：
影响因子：
3.3
通讯作者：
Goto, S.
中科院分区：
文献类型：
--
作者：
Okita, S.;Morigaki, R.;Goto, S.
亨廷顿病（HD）的纹状体神经病理学涉及中等大小投射神经元的原发性和进行性变性，局部回路中间神经元相对较少。HD纹状体中这种模式化细胞丢失的机制仍然不清楚。视神经磷酸酶（OPTN）是与亨廷顿蛋白相互作用的蛋白质之一，在几种神经退行性疾病中起保护作用。为了确定OPTN在小鼠纹状体中的细胞定位模式，我们采用了具有酪胺信号放大系统的高灵敏度免疫组织化学。在这项研究中，我们表明，OPTN出现作为一个细胞质蛋白的纹状体神经元的子集内。特别令人感兴趣的是，OPTN在中间神经元中大量表达，而在中间投射神经元中观察到低水平的OPTN。OPTN在纹状体中的这种细胞类型特异性分布与HD患者纹状体中通常观察到的神经元损失模式惊人地互补。我们认为，OPTN丰度是一个重要的细胞因素，在考虑特定类型的细胞在HD纹状体神经元的脆弱性。(C)2011年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Striatal neuropathology of Huntington's disease (HD) involves primary and progressive degeneration of the medium-sized projection neurons, with relative sparing of the local circuit interneurons. The mechanism for such a patterned cell loss in the HD striatum continues to remain unclear. Optineurin (OPTN) is one of the proteins interacting with huntingtin and plays a protective role in several neuro-degenerative disorders. To determine the cellular localization pattern of OPTN in the mouse striatum, we employed a highly sensitive immunohistochemistry with the tyramide signal amplification system. In this study, we show that OPTN appeared as a cytoplasmic protein within the subsets of the striatal neurons. Of particular interest was that OPTN was abundantly expressed in the interneurons, whereas low levels of OPTN were observed in the medium projection neurons. This cell type-specific distribution of OPTN in the striatum is strikingly complementary to the pattern of neuronal loss typically observed in the striatum of patients with HD. We suggest that OPTN abundance is an important cellular factor in considering the cell type-specific vulnerability of striatal neurons in HD. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.