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亨廷顿病 R6/2 小鼠模型脑内神经球蛋白的定位。

Localization of neuroglobin in the brain of R6/2 mouse model of Huntington's disease.

机构信息

Department of Science, Roma Tre University, Rome, Italy.

Santa Lucia Foundation IRCCS, Rome, Italy.

出版信息

Neurol Sci. 2018 Feb;39(2):275-285. doi: 10.1007/s10072-017-3168-2. Epub 2017 Nov 3.

DOI:10.1007/s10072-017-3168-2
PMID:29101592
Abstract

Neuroglobin (Ngb) is expressed in the central and peripheral nervous system, cerebrospinal fluid, retina, and endocrine tissues where it is involved in binding O and other gasotransmitters. Several studies have highlighted its endogenous neuroprotective function. Huntington's disease (HD), a dominant hereditary disease, is characterized by the gradual loss of neurons in discrete areas of the central nervous system. We analyzed the expression of Ngb in the brain tissue of a mouse model of HD, in order to define the role of Ngb with respect to individual cell type vulnerability in HD and to gender and age of mice. Our results showed different expressions of Ngb among neurons of a specific region and between different brain regions. We evidenced a decreased intensity of Ngb at 13 weeks of age, compared to 7 weeks of age. The double immunofluorescence and fluorescence resonance energy transfer (FRET) experiments showed that the co-localization between Ngb and huntingtin at the subcellular level was not close enough to account for a direct interaction. We also observed a different expression of Ngb in the striatum, depending on the sex and age of animals. These findings provide the first experimental evidence for an adaptive response of Ngb in HD, suggesting that Ngb may exert neuroprotective effects in HD beyond its role in reducing sensitivity to oxidative stress.

摘要

神经球蛋白(Ngb)在中枢和外周神经系统、脑脊液、视网膜和内分泌组织中表达,参与与 O 和其他气体递质的结合。多项研究强调了其内源性神经保护功能。亨廷顿病(HD)是一种显性遗传性疾病,其特征是中枢神经系统的离散区域中的神经元逐渐丧失。我们分析了 HD 小鼠模型脑组织中 Ngb 的表达情况,以便确定 Ngb 在 HD 中与个体细胞类型易感性以及与性别和年龄相关的作用。我们的结果表明,在特定区域的神经元之间以及不同脑区之间,Ngb 的表达存在差异。与 7 周龄相比,我们在 13 周龄时发现 Ngb 的强度降低。双重免疫荧光和荧光共振能量转移(FRET)实验表明,亚细胞水平上 Ngb 和亨廷顿之间的共定位不够紧密,无法解释直接相互作用。我们还观察到纹状体中 Ngb 的表达因动物的性别和年龄而异。这些发现为 HD 中 Ngb 的适应性反应提供了首个实验证据,表明 Ngb 可能在其降低对氧化应激敏感性的作用之外,在 HD 中发挥神经保护作用。

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