Apical dendrite degeneration, a novel cellular pathology for Betz cells in ALS
Apical dendrite degeneration, a novel cellular pathology for Betz cells in ALS
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DOI：
10.1038/srep41765
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发表时间：
2017-02-06
影响因子：
4.6
通讯作者：
Ozdinler, P. Hande
中科院分区：
文献类型：
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作者：
Genc, Baris;Jara, Javier H.;Ozdinler, P. Hande
Betz 细胞的顶端树突是皮质输入整合的重要部位，但其健康状况尚未在 ALS 患者中得到充分评估。我们研究了从死后正常对照受试者、家族性 ALS (fALS)、散发性 ALS (sALS)、ALS 伴额颞叶痴呆 (FTD-ALS) 和阿尔茨海默病 (AD) 中分离的初级运动皮质，发现 fALS 和 sALS 以及 FTD-ALS 患者中 Betz 细胞存在严重的顶端树突变性。相比之下，AD 患者和正常对照组的 Betz 细胞保留了运动皮层中的细胞完整性，并且 CA1 锥体神经元主要在其胞体中表现出异常，而不是顶端树突。与广泛的空泡形成和细胞结构瓦解相一致，仅 ALS 患者的突触数量也显着减少。我们的研究结果表明顶端树突变性是一种新的细胞病理学，可以区分 ALS，并进一步支持皮质功能障碍对于疾病病理学的重要性。
Apical dendrites of Betz cells are important sites for the integration of cortical input, however their health has not been fully assessed in ALS patients. We investigated the primary motor cortices isolated from post-mortem normal control subjects, patients with familial ALS (fALS), sporadic ALS (sALS), ALS with frontotemporal dementia (FTD-ALS), and Alzheimer's disease (AD), and found profound apical dendrite degeneration of Betz cells in both fALS and sALS, as well as FTD-ALS patients. In contrast, Betz cells of AD patients and normal controls retain cellular integrity in the motor cortex, and CA1 pyramidal neurons show abnormalities predominantly within their soma, rather than the apical dendrite. In line with extensive vacuolation and cytoarchitectural disintegration, the numbers of synapses were also significantly reduced only in ALS patients. Our findings indicate apical dendrite degeneration as a novel cellular pathology that distinguishes ALS and further support the importance of cortical dysfunction for disease pathology.