Heterotopic Purkinje Cells: a Comparative Postmortem Study of Essential Tremor and Spinocerebellar Ataxias 1, 2, 3, and 6
Heterotopic Purkinje Cells: a Comparative Postmortem Study of Essential Tremor and Spinocerebellar Ataxias 1, 2, 3, and 6
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DOI：
10.1007/s12311-017-0876-3
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发表时间：
2018-04-01
期刊：
影响因子：
3.5
通讯作者：
Faust, Phyllis L.
中科院分区：
文献类型：
--
作者：
Louis, Elan D.;Kuo, Sheng-Han;Faust, Phyllis L.
特发性震颤（ET）是最常见的神经系统疾病之一。死后研究注意到ET小脑的一系列病理变化。异位浦肯野细胞（PC）是指其细胞体错误定位在分子层中的细胞。在神经退行性环境中，这些被视为神经元变性进展的标志物。我们（1）量化ET病例与对照组的异位，（2）将ET病例与其他小脑退行性疾病（脊髓小脑共济失调（SCA）1，2，3和6）进行比较，（3）将这些SCA相互比较，（4）在每种疾病相关PC丢失的背景下评估异位。使用标准LH& E染色的新小脑切片定量异位PC。将计数标准化为PC层长度（n-异位计数）。在评估异位时，考虑PC计数也是有价值的，因为PC的丢失延伸到正常位置以及异位PC。因此，我们将n-异位除以PC计数。共有96个大脑（43个ET、31个SCA [12个SCA 1、7个SCA 2、7个SCA 3、5个SCA 6]和22个对照）。ET组的n-异位中位数是对照组的2倍（2.6 vs.1.2，p < 0.05）。各种SCA中的n-异位的中位数形成了一个谱，SCA 3和SCA 1中的计数最高。在考虑PC计数的分析中，ET的n-异位/浦肯野细胞计数中位数是对照组的3倍（0.35 vs. 0.13，p < 0.01），SCA 1和SCA 2的计数分别是对照组的5.5和11倍（分别p < 0.001）。ET组的n-异位/PC计数中位数介于对照组和SCA组之间。同样，ET中PC计数的中位数介于对照组和SCA组之间; SCA 3是一个例外，众所周知，SCA 3中PC人群得以保留。异位是ET的疾病相关特征。相比之下，几个SCA证明甚至更显着的异位，虽然频谱存在于整个SCA。ET的n-异位/PC计数中位数和PC中位数介于对照组和SCA组之间;因此，在这方面，ET可能代表脊髓小脑萎缩的中间状态或较不晚期状态。
Essential tremor (ET) is among the most common neurological diseases. Postmortem studies have noted a series of pathological changes in the ET cerebellum. Heterotopic Purkinje cells (PCs) are those whose cell body is mis-localized in the molecular layer. In neurodegenerative settings, these are viewed as a marker of the progression of neuronal degeneration. We (1) quantify heterotopias in ET cases vs. controls, (2) compare ET cases to other cerebellar degenerative conditions (spinocerebellar ataxias (SCAs) 1, 2, 3, and 6), (3) compare these SCAs to one another, and (4) assess heterotopia within the context of associated PC loss in each disease. Heterotopic PCs were quantified using a standard LH&E-stained section of the neocerebellum. Counts were normalized to PC layer length (n-heterotopia count). It is also valuable to consider PC counts when assessing heterotopia, as loss of PCs extends both to normally located as well as heterotopic PCs. Therefore, we divided n-heterotopias by PC counts. There were 96 brains (43 ET, 31 SCA [12 SCA1, 7 SCA2, 7 SCA3, 5 SCA6], and 22 controls). The median number of n-heterotopias in ET cases was two times higher than that of the controls (2.6 vs. 1.2, p < 0.05). The median number of n-heterotopias in the various SCAs formed a spectrum, with counts being highest in SCA3 and SCA1. In analyses that factored in PC counts, ET had a median n-heterotopia/Purkinje cell count that was three times higher than the controls (0.35 vs. 0.13, p < 0.01), and SCA1 and SCA2 had counts that were 5.5 and 11 times higher than the controls (respective p < 0.001). The median n-heterotopia/PC count in ET was between that of the controls and the SCAs. Similarly, the median PC count in ET was between that of the controls and the SCAs; the one exception was SCA3, in which the PC population is well known to be preserved. Heterotopia is a disease-associated feature of ET. In comparison, several of the SCAs evidenced even more marked heterotopia, although a spectrum existed across the SCAs. The median n-heterotopia/PC count and median PC in ET was between that of the controls and the SCAs; hence, in this regard, ET could represent an intermediate state or a less advanced state of spinocerebellar atrophy.