Age-dependent synuclein pathology following traumatic brain injury in mice
Age-dependent synuclein pathology following traumatic brain injury in mice
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DOI：
10.1016/s0014-4886(03)00245-0
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发表时间：
2003-11-01
影响因子：
5.3
通讯作者：
Trojanowski, JQ
中科院分区：
文献类型：
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作者：
Uryu, K;Giasson, BI;Trojanowski, JQ
突触蛋白(Syn)是一类突触蛋白家族，包括α-Syn，它通过形成不同的大脑病理(路易小体和神经突起)，在帕金森氏病和相关的神经退行性疾病(突触核病)中发挥关键作用。由于创伤性脑损伤(TBI)是帕金森氏病的一个鲜为人知的危险因素，我们研究了年轻和老年小鼠脑中TBI对α-、β-和伽马-Syn的影响。免疫组织化学分析显示，青年和老年假损伤小鼠的大脑皮质、纹状体和海马神经纤维层的α-和β-Syn免疫反应(LR)正常，很少或没有Gamma-Syn免疫反应。脑损伤后1周，老龄小鼠脑皮质下轴突和皮质下轴突中α-和β-Syn免疫反应增强，皮质下轴突中γ-Syn免疫反应增强。这与α-Syn中改变的或硝化的表位的抗体以及诱导型一氧化氮合酶的抗体对纹状体轴突束的强烈标记有关。然而，这些由脑损伤引起的变化在脑损伤后16周消失，并且在接受脑损伤的幼鼠和α-Syn基因敲除小鼠中都没有发现Syn IR的改变，而Western blotting证实，脑损伤导致小鼠大脑中α-Syn的一过性改变。这种年龄依赖的脑损伤诱导的阿尔法-突触核一过性改变的模型提供了一个机会来研究脑损伤与联核病的疾病机制之间的可能联系。(C)2003年埃尔塞维尔科学公司(美国)。版权所有。
Synucleins (Syn), a family of synaptic proteins, includes alpha-Syn, which plays a pivotal role in Parkinson's disease and related neurodegenerative diseases (synucleinopathics) by forming distinct brain pathologies (Lewy bodies and neurites). Since traumatic brain injury (TBI) is a poorly understood risk factor for Parkinson's disease, we examined the effects of TBI in the young and aged mouse brain on alpha-, beta-, and gamma-Syn. Immunohistochemical analysis showed that brains from sham-injured young and aged mice had normal alpha- and beta-Syn immunoreactivity (lR) in neuropil of cortex, striatum, and hippocampus with little or no gamma-Syn IR. At 1 week post TBI, the aged mouse brain showed a transient increase of alpha- and beta-Syn IR in the neuropil as well as an induction of gamma-Syn IR in subcortical axons. This was associated with strong labeling of striatal axon bundles by antibodies to altered or nitrated epitopes in a-Syn as well as by antibodies to inducible nitric oxide synthase. However, these TBI-induced changes disappeared by 16 weeks post TBI, and altered Syn IR was not seen in young mice subjected to TBI nor in alpha-Syn knockout mice while Western blots confirmed that TBI induced transient alterations of alpha-Syn in the mouse brains. This model of age-dependent TBI-induced transient alterations in alpha-Syn provides an opportunity to examine possible links between TBI and mechanisms of disease in synucleinopathies. (C) 2003 Elsevier Science (USA). All rights reserved.