Department of Neurology, University of Texas Southwestern, 5323 Harry Hines Blvd, Dallas, TX, 75390-8813, USA.
Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Cerebellum. 2024 Dec;23(6):2383-2396. doi: 10.1007/s12311-024-01739-1. Epub 2024 Sep 4.
Under stress, Purkinje cells (PCs) undergo a variety of reactive morphological changes. These can include swellings of neuronal processes. While axonal swellings, "torpedoes", have been well-studied, dendritic swellings (DS) have not been the centerpiece of study. Surprisingly little is known about their frequency or relationship to other morphological changes in degenerating PCs. Leveraging a large brain bank, we (1) examined the morphology of DS, (2) quantified DS, and (2) examined correlations between counts of DS versus 16 other PC morphological changes in a broad range of cerebellar degenerative disorders. There were 159 brains - 100 essential tremor (ET), 13 Friedreich's ataxia, and 46 spinocerebellar ataxia (SCA) (14 SCA1, 7 SCA2, 13 SCA3, 5 SCA6, 5 SCA7, and 2 SCA8). DS were a feature of PCs across all these disorders, with varying morphologies and changes elsewhere in the dendritic arbor. On Luxol fast blue/hematoxylin and eosin-stained sections, the median number of DS per PC ranged from 0.001 in ET to 0.025 in SCA8. Bielschowsky-stained sections yielded higher counts, from 0.003 in ET to 0.042 in SCA6. Torpedo counts exceeded DS counts by one order of magnitude. DS counts were more robustly correlated with torpedo counts than with counts for any of the other PC morphological changes. In summary, DS ranged in prevalence across cerebellar degenerative disorders, from 1/1,000 to 42/1,000 PCs. Across disorders of cerebellar degeneration, these swellings of the dendritic compartment were most robustly correlated with swellings of the axonal compartment, suggesting a similar type of cellular response to duress.
在压力下，浦肯野细胞（PC）会发生多种反应性形态变化。这些变化可能包括神经元突起肿胀。虽然轴突肿胀，即“鱼雷”，已经得到了很好的研究，但树突肿胀（DS）并不是研究的重点。令人惊讶的是，人们对它们的频率或与退化 PC 中其他形态变化的关系知之甚少。利用一个大型脑库，我们 (1) 检查了 DS 的形态，(2) 对 DS 进行了量化，(2) 检查了 DS 计数与其他 16 种 PC 形态变化之间的相关性，这些变化存在于广泛的小脑退行性疾病中。共有 159 个大脑——100 个特发性震颤（ET）、13 个弗里德里希共济失调和 46 个脊髓小脑共济失调（SCA）（14 个 SCA1、7 个 SCA2、13 个 SCA3、5 个 SCA6、5 个 SCA7 和 2 个 SCA8）。DS 是所有这些疾病中 PC 的特征，其形态和树突分支的其他部位的变化各不相同。在洛索夫快速蓝/苏木精和伊红染色切片上，每 PC 的 DS 中位数范围从 ET 的 0.001 到 SCA8 的 0.025。比尔斯洛斯基染色切片的计数更高，从 ET 的 0.003 到 SCA6 的 0.042。鱼雷计数比 DS 计数高一个数量级。DS 计数与鱼雷计数的相关性比与任何其他 PC 形态变化的相关性都更稳健。总之，DS 在小脑退行性疾病中的患病率从 1/1000 到 42/1000 PC 不等。在小脑退行性疾病中，这些树突节段的肿胀与轴突节段的肿胀最为密切相关，这表明细胞对压力的反应类型相似。
