p75NTR independent oligodendrocyte death in cuprizone-induced demyelination in C57BL/6 mice
p75NTR independent oligodendrocyte death in cuprizone-induced demyelination in C57BL/6 mice
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DOI：
10.1111/j.1365-2990.2005.00656.x
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发表时间：
2005-12-01
影响因子：
5
通讯作者：
Boddeke, HWGM
中科院分区：
文献类型：
--
作者：
Copray, JCVM;Küst, BM;Boddeke, HWGM
喂食C57 Bl/6 J小鼠的铜螯合剂cuprizone导致成熟少突胶质细胞的选择性凋亡和伴随的主要在胼胝体中的脱髓鞘。在多发性硬化症（MS）的动物模型中，少突胶质细胞凋亡的过程涉及早期小胶质细胞活化，但没有T淋巴细胞浸润。因此，该模型可以模拟少突胶质细胞变性的早期阶段。受影响的少突胶质细胞表达常见的神经营养因子受体p75（NTR），这是一种在某些情况下可以诱导细胞凋亡的“应激受体”。仅MS病变和MS动物模型中受影响的少突胶质细胞表达该受体。为了研究p75（NTR）在少突胶质细胞命运中的意义，我们将野生型和p75（NTR）基因敲除小鼠暴露于0.2%（w/w）的铜腙饮食中，并在不同时间点对胼胝体进行比较免疫组织化学分析。令人惊讶的是，我们的研究结果表明，p75（NTR）的情况下，并没有改变cuprizone诱导的少突胶质细胞死亡（和随后的脱髓鞘或髓鞘再生）。显然，在缺乏T淋巴细胞和T淋巴细胞衍生的细胞因子的情况下，成年少突胶质细胞中的细胞内凋亡途径不需要p75（NTR）激活的信号转导。
Feeding C57Bl/6 J mice the copper chelator cuprizone leads to selective apoptosis of mature oligodendrocytes and concomitant demyelination predominantly in the corpus callosum. The process of oligodendrocyte apoptosis in this animal model for multiple sclerosis (MS) involves early microglial activation, but no infiltration of T-lymphocytes. Therefore, this model could mimic early stages of oligodendrocyte degeneration Affected oligodendrocytes express the common neurotrophin receptor, p75(NTR), a 'stress-receptor' which under certain circumstances can induce apoptosis. Only affected oligodendrocytes in MS lesions and MS animal models express this receptor. In order to study the significance of p75(NTR) in the fate of oligodendrocytes, we have exposed wild-type as well as p75(NTR)-knockout mice to a 0.2% (w/w) cuprizone diet and performed a comparative immunohistochemical analysis of the corpus callosum at various time points. Surprisingly, our results show that the absence of p75(NTR) did not alter cuprizone-induced oligodendrocyte death (and subsequent de- or remyelination). Apparently, intracellular apoptosis pathways in adult oligodendrocytes do not require p75(NTR) activated signal transduction in the absence of T-lymphocytes and T-lymphocyte derived cytokines.