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阿尔茨海默病延髓严重的 tau 病和轴索性神经病提示自主神经功能改变。

Severe tauopathy and axonopathy in the medulla oblongata in Alzheimer's disease implicate the changes in autonomic nervous function.

机构信息

Wuhan Institute for Neuroscience and Neuroengineering, South-Central Minzu University, Wuhan, Hubei, China; The College of Life Sciences, South-Central Minzu University, Wuhan, Hubei, China.

Tongji University School of Medicine, Shanghai, China.

出版信息

J Chem Neuroanat. 2022 Sep;123:102105. doi: 10.1016/j.jchemneu.2022.102105. Epub 2022 May 11.

DOI:10.1016/j.jchemneu.2022.102105
PMID:35568249
Abstract

The autonomic dysfunctions in Alzheimer's disease (AD) have been identified from many clinical studies, however, there is still a lack of evidence directly verifying the structural abnormalities of the autonomic nervous system in AD. Human medulla oblongatas from four AD patients or five non-AD subjects were obtained and observed by using immunohistochemical staining of hyperphosphorylated tau and Aβ amyloid, and post-mortem tracing techniques. We found distinct axonal and somatic immunoreactivities for the tau markers AT8 and Tau-5 in the different areas of the medulla oblongata in AD patients, which was particularly obvious in the dorsal nucleus of the vagus nerve, the nucleus of the solitary tract and the reticular nucleus. The swollen axons, which are a typical feature of axonopathy, were not only identified in the axons with immunohistochemical labeling of AT8 and Tau-5 in the different nuclei of the medulla oblongata, but also in the tracer-labeled afferent and efferent fibres of the vagus nerve in AD patients. Such changes in tauopathy and axonopathy were only occasionally found in the non-AD aged subjects. Interestingly, we did not observe any intra- or extracellular Aβ deposits in the medulla oblongatas of the AD patients or of the non-AD subjects. These results in small samples suggest that occurrence of tauopathy and axonopathy in the parasympathetic nuclei of the medulla oblongata in AD patients may implicate the change of autonomic nervous function.

摘要

阿尔茨海默病(AD)的自主神经功能障碍已在许多临床研究中得到证实,但仍缺乏直接证实 AD 患者自主神经系统结构异常的证据。我们从 4 名 AD 患者和 5 名非 AD 患者的延髓中获取样本,通过对磷酸化 tau 和 Aβ 淀粉样蛋白的免疫组织化学染色和死后示踪技术进行观察。我们发现 AD 患者延髓的不同区域存在 tau 标志物 AT8 和 Tau-5 的明显轴突和体免疫反应性,在迷走神经背核、孤束核和网状核中尤为明显。肿胀的轴突是轴突病的典型特征,不仅在 AT8 和 Tau-5 免疫组织化学标记的不同核内的轴突中被识别,而且在 AD 患者的迷走神经传入和传出纤维中也被识别。这种 tau 病和轴突病的变化在非 AD 老年患者中偶尔发现。有趣的是,我们在 AD 患者或非 AD 患者的延髓中均未观察到任何细胞内或细胞外的 Aβ 沉积。这些小样本的结果表明,AD 患者延髓副交感神经核中 tau 病和轴突病的发生可能暗示自主神经功能的改变。

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1
Severe tauopathy and axonopathy in the medulla oblongata in Alzheimer's disease implicate the changes in autonomic nervous function.阿尔茨海默病延髓严重的 tau 病和轴索性神经病提示自主神经功能改变。
J Chem Neuroanat. 2022 Sep;123:102105. doi: 10.1016/j.jchemneu.2022.102105. Epub 2022 May 11.
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The origin and development of plaques and phosphorylated tau are associated with axonopathy in Alzheimer's disease.斑块和磷酸化 tau 的起源和发展与阿尔茨海默病中的轴突病变有关。
Neurosci Bull. 2011 Oct;27(5):287-99. doi: 10.1007/s12264-011-1736-7.
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Axonopathy Likely Initiates Neuropathological Processes Via a Mechanism of Axonal Leakage in Alzheimer's Mouse Models.轴突病可能通过阿尔茨海默病小鼠模型中的轴突渗漏机制引发神经病理学过程。
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The autonomic higher order processing nuclei of the lower brain stem are among the early targets of the Alzheimer's disease-related cytoskeletal pathology.脑干下部的自主神经高阶处理核是阿尔茨海默病相关细胞骨架病理的早期靶点之一。
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Projections from the nucleus tractus solitarii to the rostral ventrolateral medulla.从孤束核到延髓头端腹外侧区的投射。
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