Purkinje cell axonal anatomy: quantifying morphometric changes in essential tremor versus control brains
Purkinje cell axonal anatomy: quantifying morphometric changes in essential tremor versus control brains
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DOI：
10.1093/brain/awt238
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发表时间：
2013-10-01
期刊：
影响因子：
14.5
通讯作者：
Louis, Elan D.
中科院分区：
文献类型：
--
作者：
Babij, Rachel;Lee, Michelle;Louis, Elan D.
越来越多的临床、神经影像学和尸检数据表明小脑在特发性震颤的发病机制中起着重要作用。除了在一些尸检研究中浦肯野细胞的适度减少外，特发性震颤病例中的浦肯野细胞轴突索（鱼雷）比对照组更大程度地存在。然而，浦肯野细胞轴突室中更微妙的形态学变化的详细研究尚未进行。我们进行了详细的形态学分析的浦肯野细胞轴突室在49原发性震颤和39个对照组的大脑，使用钙结合蛋白D-28 K免疫组织化学100 μ m小脑皮质vibratome组织切片。与对照组相比，特发性震颤病例中轴突形状的变化[轴突轮廓增厚（P = 0.006），鱼雷状（P = 0.038）]和轴突连接的变化[轴突复发侧支（P <0.001），轴突分支（P <0.001），终末轴突发芽（P < 0.001）]均增加。在发病年龄> 40岁的特发性震颤病例中，形状和连通性的变化显著相关[例如，增厚的轴突轮廓与复发侧支之间的相关性（r = 0.405，P < 0.001）]，并且与震颤持续时间相关。在特发性震颤的情况下，增厚的轴突轮廓，轴突复发侧支和分支轴突上的浦肯野细胞的鱼雷与浦肯野细胞没有鱼雷的轴突更频繁地看到3至5倍。我们记录了原发性震颤中浦肯野细胞轴突室的一系列变化。其中一些可能是对浦肯野细胞损伤的代偿性变化，从而说明浦肯野细胞的一个重要特征，即它们对损伤具有相对抵抗力，并能够动员广泛的轴突对损伤的反应。浦肯野细胞轴突的这种可塑性在多大程度上是部分神经保护性的，或者在减缓进一步的细胞变化和细胞死亡方面最终是无效的，值得在特发性震颤中进一步研究。
Growing clinical, neuro-imaging and post-mortem data have implicated the cerebellum as playing an important role in the pathogenesis of essential tremor. Aside from a modest reduction of Purkinje cells in some post-mortem studies, Purkinje cell axonal swellings (torpedoes) are present to a greater degree in essential tremor cases than controls. Yet a detailed study of more subtle morphometric changes in the Purkinje cell axonal compartment has not been undertaken. We performed a detailed morphological analysis of the Purkinje cell axonal compartment in 49 essential tremor and 39 control brains, using calbindin D-28k immunohistochemistry on 100-mu m cerebellar cortical vibratome tissue sections. Changes in axonal shape [thickened axonal profiles (P = 0.006), torpedoes (P = 0.038)] and changes in axonal connectivity [axonal recurrent collaterals (P < 0.001), axonal branching (P < 0.001), terminal axonal sprouting (P < 0.001)] were all present to an increased degree in essential tremor cases versus controls. The changes in shape and connectivity were significantly correlated [e.g. correlation between thickened axonal profiles and recurrent collaterals (r = 0.405, P < 0.001)] and were correlated with tremor duration among essential tremor cases with age of onset > 40 years. In essential tremor cases, thickened axonal profiles, axonal recurrent collaterals and branched axons were 3- to 5-fold more frequently seen on the axons of Purkinje cells with torpedoes versus Purkinje cells without torpedoes. We document a range of changes in the Purkinje cell axonal compartment in essential tremor. Several of these are likely to be compensatory changes in response to Purkinje cell injury, thus illustrating an important feature of Purkinje cells, which is that they are relatively resistant to damage and capable of mobilizing a broad range of axonal responses to injury. The extent to which this plasticity of the Purkinje cell axon is partially neuroprotective or ultimately ineffective at slowing further cellular changes and cell death deserves further study in essential tremor.