TDP-43 蛋白病伴运动神经元累及的脊髓少突胶质细胞反应。
Oligodendroglial response in the spinal cord in TDP-43 proteinopathy with motor neuron involvement.
机构信息
Department of Pathology and Molecular Medicine, Thomayer Hospital, Charles University in Prague, Prague, Czech Republic.
出版信息
Neurodegener Dis. 2014;14(3):117-24. doi: 10.1159/000362929. Epub 2014 Aug 5.
BACKGROUND
TDP-43 proteinopathies represent a spectrum of neurodegenerative disorders. Variable clinical presentations including frontotemporal dementia, amyotrophic lateral sclerosis (ALS) and mixed forms are associated with the spatial heterogeneity of the TDP-43 pathology. Recent studies have emphasized the role of oligodendrocytes in the pathogenesis of ALS.
OBJECTIVE
To evaluate whether TDP-43 proteinopathies are associated with an oligodendroglial response.
METHODS
We performed a study on 7 controls and 10 diseased patients with spinal cord involvement. Using the oligodendroglia-specific antibody TPPP/p25, we assessed oligodendrocyte density in the lateral corticospinal tracts (LCSs) along with the presence of perineuronal oligodendrocytes (PNOGs) in the anterior horns. We performed a densitometry of myelin basic protein (MBP) immunoreactivity. The numbers of TDP-43 and p62 immunoreactive inclusions were counted in both the LCSs and the anterior horns.
RESULTS
Double immunolabeling confirmed that oligodendrocytes harbor TDP-43 inclusions. In the LCSs, MBP density, but not the number of oligodendrocytes, was decreased in the diseased group. However, oligodendrocyte counts in the LCS correlated positively, and the density of MBP inversely, with the number of neuronal inclusions in the anterior horn, suggestive of a compensatory response of oligodendrocytes. The number of neurons with PNOGs correlated with the amount of inclusions.
CONCLUSION
Our study further emphasizes the importance of oligodendroglia in the pathogenesis of TDP-43 proteinopathies with spinal cord involvement.
背景
TDP-43 蛋白病代表了一系列神经退行性疾病。可变的临床表现，包括额颞叶痴呆、肌萎缩侧索硬化症（ALS）和混合形式，与 TDP-43 病理学的空间异质性有关。最近的研究强调了少突胶质细胞在 ALS 发病机制中的作用。
目的
评估 TDP-43 蛋白病是否与少突胶质细胞反应有关。
方法
我们对 7 名对照和 10 名脊髓受累的患病患者进行了研究。使用少突胶质细胞特异性抗体 TPPP/p25，我们评估了外侧皮质脊髓束（LCS）中的少突胶质细胞密度以及前角中的周围神经胶质少突胶质细胞（PNOGs）的存在。我们对髓鞘碱性蛋白（MBP）免疫反应性进行了密度测定。在 LCS 和前角中，计数 TDP-43 和 p62 免疫反应性包涵体的数量。
结果
双重免疫标记证实少突胶质细胞含有 TDP-43 包涵体。在 LCS 中，病变组 MBP 密度降低，但少突胶质细胞数量不变。然而，LCS 中的少突胶质细胞计数与前角神经元包涵体的数量呈正相关，而 MBP 的密度则呈负相关，提示少突胶质细胞有代偿反应。具有 PNOGs 的神经元数量与包涵体的数量相关。
结论
我们的研究进一步强调了少突胶质细胞在 TDP-43 蛋白病伴脊髓受累发病机制中的重要性。
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