Morphological alterations in dorsal root ganglion neurons and supporting cells of organotypic mouse spinal cord-ganglion cultures exposed to taxol
Morphological alterations in dorsal root ganglion neurons and supporting cells of organotypic mouse spinal cord-ganglion cultures exposed to taxol
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暴露于紫杉醇的器官型小鼠脊髓神经节培养物的背根神经节神经元和支持细胞的形态学改变
DOI：
10.1016/0306-4522(83)90148-3
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发表时间：
1983
期刊：
影响因子：
3.3
通讯作者：
S. B. Horwitz
中科院分区：
文献类型：
--
作者：
E. B. Masurovsky;Edith R. Peterson;S. Crain;S. B. Horwitz
14 天的胎儿小鼠脊髓附着有背根神经节，在培养 2-3 周内已分化，暴露于 1-2 μM 紫杉醇长达 6 天。在接触药物期间，培养基中添加了神经生长因子（300单位/ml）。在紫杉醇中3-6天时，在神经节神经元的周围核周和近端神经炎区域中观察到异常数量的微管。微管还包围许多神经元中多形性囊泡/脑池元件的大量聚集。这些聚集体在活细胞中表现为异常的“透明”球状区域，并且通常与细胞核一样大。构成这些引人注目的囊泡/脑池积聚的一些元素似乎是通常在细胞中心周围极化的破坏的高尔基复合体的一部分，以及肥大的光滑内质网结构。在其他神经元区域，高尔基复合体和其他细胞器受到较小程度的改变或破坏。在神经元胞体和神经突中，有序的微管阵列沿着内质网池出现。随着时间的推移，大量的微管以各种方向聚集在整个核周，显然与微管组织中心无关。与与微管蛋白相互作用的其他植物生物碱的作用不同，尽管细丝的分布似乎发生了变化，但细丝没有明显的增加。同心有序的微管-大分子层状复合物仅在神经突中可见。神经元细胞核畸形，经常移位，并显示出让人想起色谱溶解的精细结构。卫星细胞和雪旺细胞含有异常丰富的微管、异常的池、破坏的高尔基复合体和增加的溶酶体。一些细胞核显示出异常的染色质，在极少数情况下甚至显示出微管。我们认为紫杉醇通过在这些细胞的异常分组和异常位置中产生异常丰富的微管来改变背根神经节细胞中细胞器系统的分布、完整性和/或组织。
Expiants of 14-day fetal mouse spinal cord with attached dorsal root ganglia, which had become differentiated over 2–3 weeks in culture, were exposed to 1–2 μM taxol for up to 6 days. The culture medium was supplemented with nerve growth factor (300 units/ml) during exposure to the drug.By 3–6 days in taxol, unusually numerous microtubules were seen in peripheral perikaryal and proximal neuritic regions of ganglion neurons. Microtubules also engirdled massive aggregations of pleomorphic vesicular/cisternal elements in many neurons. These aggregates were visible as unusual ‘clear’ spheroidal regions in the living cells, and were often as large as the nuclei. Some of the elements comprising these striking vesicular/cisternal accumulations appeared to be portions of disrupted Golgi complexes normally polarized around the cytocentrum, as well as hypertrophied smooth endoplasmic reticulum formations. In other neuronal areas, Golgi complexes and other organelles were altered or disrupted to lesser degrees. Ordered microtubular arrays occurred along endoplasmic reticulum cisternae both in neuron somata and neurites. Over time, a plethora of microtubules assembled throughout the perikarya in various orientations apparently unrelated to microtubule organizing centers. Unlike the effects of other plant alkaloids that interact with tubulin, there was no discernible increase in filaments, although their distribution appeared altered. Concentric ordered microtubular-macromolecular lamellated complexes were seen only in neurites. Neuronal nuclei were misshapen, often displaced, and displayed fine structure reminiscent of chromatolysis. Satellite and Schwann cells contained atypically abundant microtubules, abnormal cisternae, disrupted Golgi complexes, and increased lysosomes. Some nuclei displayed abnormal chromatin, and in rare cases even microtubules.We suggest that taxol alters the distribution, integrity, and/or organization of organelle systems in dorsal root ganglion cells by engendering unusually abundant microtubules in abnormal groupings and aberrant locations in these cells.