摘要
人类脑干参与睡眠/清醒周期的调节与正常睡眠的系统,决定着各种运动、至关重要的自主神经、动眼神经、前庭、听觉,摄食和体觉功能的性能。它是升高多巴胺能、胆碱能、去甲肾上腺素、5-羟色胺能系统的起源,以及下降5-羟色胺能系统的基地。与大脑皮层对比,仅仅大约40年前最初的脑干的研究才认识到阿尔茨海默氏病(AD)通过神经元纤维或tau蛋白细胞骨架病理的脑干的影响。银染色或tau蛋白免疫组化染色进行病理解剖研究脑干组织切片显示在中缝核、蓝斑核,并在黑质和脑桥核的致密部分神经细胞的损失和突出的与AD相关的细胞骨架的变化。AD患者的听觉脑干系统(即下丘、上橄榄核、耳蜗背侧核)、动眼神经脑干网络(即内侧纵束的喙间质核、Edinger-Westphal核、脑桥网状被盖核)、自主神经系统(即中央导水管周围灰质、臂旁核、巨细胞网状核、迷走神经背核和孤核,中间网状带)还检测到额外明显的与AD相关的细胞骨架病理改变。这些脑干核团的变化首次能充分地解释AD患者各种费解的疾病症状:帕金森锥体束外运动症状、抑郁、幻觉,睡眠/觉醒周期的紊乱、睡眠习惯的改变,注意力缺陷,过大的瞳孔扩张、自主神经功能障碍、水平和垂直扫视运动障碍,平滑追随运动障碍。某些脑干核很早期的发生与AD相关的的细胞骨架病理,表明脑干在与AD相关的细胞骨架病理的诱导和脑扩散的重要的作用。
关键词: 阿尔茨海默病,脑干,细胞骨架的病理学,病理解剖学,tau蛋白。
Current Alzheimer Research
Title:The Brainstem Tau Cytoskeletal Pathology of Alzheimer’s Disease: A Brief Historical Overview and Description of its Anatomical Distribution Pattern, Evolutional Features, Pathogenetic and Clinical Relevance
Volume: 13 Issue: 10
Author(s): Udo Rüb, Katharina Stratmann, Helmut Heinsen, Domenico Del Turco, Kay Seidel, Wilfred den Dunnen, Horst-Werner Korf
Affiliation:
关键词: 阿尔茨海默病,脑干,细胞骨架的病理学,病理解剖学,tau蛋白。
摘要: The human brainstem is involved in the regulation of the sleep/waking cycle and normal sleep architectonics and is crucial for the performance of a variety of somatomotor, vital autonomic, oculomotor, vestibular, auditory, ingestive and somatosensory functions. It harbors the origins of the ascending dopaminergic, cholinergic, noradrenergic, serotonergic systems, as well the home base of the descending serotonergic system. In contrast to the cerebral cortex the affection of the brainstem in Alzheimer’s disease (AD) by the neurofibrillary or tau cytoskeletal pathology was recognized only approximately fourty years ago in initial brainstem studies. Detailed pathoanatomical investigations of silver stained or tau immunostained brainstem tissue sections revealed nerve cell loss and prominent ADrelated cytoskeletal changes in the raphe nuclei, locus coeruleus, and in the compact parts of the substantia nigra and pedunculopontine nucleus. An additional conspicuous AD-related cytoskeletal pathology was also detected in the auditory brainstem system of AD patients (i.e. inferior colliculus, superior olive, dorsal cochlear nucleus), in the oculomotor brainstem network (i.e. rostral interstitial nucleus of the medial longitudinal fascicle, Edinger-Westphal nucleus, reticulotegmental nucleus of pons), autonomic system (i.e. central and periaqueductal grays, parabrachial nuclei, gigantocellular reticular nucleus, dorsal motor vagal and solitary nuclei, intermediate reticular zone). The alterations in these brainstem nuclei offered for the first time adequate explanations for a variety of less understood disease symptoms of AD patients: Parkinsonian extrapyramidal motor signs, depression, hallucinations, dysfunctions of the sleep/wake cycle, changes in sleeping patterns, attentional deficits, exaggerated pupil dilatation, autonomic dysfunctions, impairments of horizontal and vertical saccades, dysfunctional smooth pursuits. The very early occurrence of the AD-related cytoskeletal pathology in some of these brainstem nuclei points to a major and strategic role of the brainstem in the induction and brain spread of the AD-related cytoskeletal pathology.
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Udo Rüb, Katharina Stratmann, Helmut Heinsen, Domenico Del Turco, Kay Seidel, Wilfred den Dunnen, Horst-Werner Korf , The Brainstem Tau Cytoskeletal Pathology of Alzheimer’s Disease: A Brief Historical Overview and Description of its Anatomical Distribution Pattern, Evolutional Features, Pathogenetic and Clinical Relevance, Current Alzheimer Research 2016; 13 (10) . https://dx.doi.org/10.2174/1567205013666160606100509
DOI https://dx.doi.org/10.2174/1567205013666160606100509 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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