Microglial Activation Induces Generation of Oligodendrocyte Progenitor Cells from the Subventricular Zone after Focal Demyelination in the Corpus Callosum
Microglial Activation Induces Generation of Oligodendrocyte Progenitor Cells from the Subventricular Zone after Focal Demyelination in the Corpus Callosum
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DOI：
10.1159/000486332
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发表时间：
2018-01-01
影响因子：
2.9
通讯作者：
Ishizaki, Yasuki
中科院分区：
文献类型：
--
作者：
Naruse, Masae;Shibasaki, Koji;Ishizaki, Yasuki
在正常生理条件下，室管膜下区（SVZ）的神经干细胞（NSCs）来源的神经母细胞可沿吻侧迁移流沿着迁移至嗅球，产生中间神经元。当脱髓鞘发生时，SVZ中的NSC或神经祖细胞（NPC）为脱髓鞘病变提供新形成的少突胶质细胞。在脱髓鞘病变的影响下，NSC/NPC谱系的可塑性可能趋向于少突分化。然而，其机制仍然未知。这项研究表明，胼胝体中的局灶性脱髓鞘引起小胶质细胞的激活，不仅在脱髓鞘部位，而且在SVZ中，并显着增加SVZ中少突胶质细胞祖细胞（OPCs）的生成。此外，米诺环素处理抑制小胶质细胞活化减少了SVZ中OPC的产生，表明由胼胝体中的局灶性脱髓鞘诱导的SVZ中的小胶质细胞活化原位调节NSC/NPC谱系可塑性。与有关胼胝体脱髓鞘的发现相反，诱导内囊局灶性脱髓鞘并没有诱导SVZ中小胶质细胞活化或OPC的产生。这些结果表明，在诱导脱髓鞘病变后，SVZ中OPC产生的机制在脱髓鞘区域之间可能是不同的。(c)2018 S. Karger AG，巴塞尔。
Neuroblasts derived from neural stem cells (NSCs) in the subventricular zone (SVZ) migrate along the rostral migratory stream into the olfactory bulb to generate interneurons under normal physiological conditions. When demyelination occurs, NSCs or neural progenitor cells (NPCs) in the SVZ provide newly formed oligodendrocytes to demyelinated lesions. The plasticity of NSC/NPC lineages may tend to oligodendrogenesis under the influence of demyelinated lesions. The mechanisms, however, still remain unknown. This study revealed that focal demyelination in the corpus callosum caused activation of the microglia, not only at the site of demyelination but also in the SVZ, and dramatically increased the generation of oligodendrocyte progenitor cells (OPCs) in the SVZ. Furthermore, the inhibition of microglial activation by minocycline treatment decreased OPC generation in the SVZ, suggesting that microglial activation in the SVZ, induced by the focal demyelination in the corpus callosum, regulates NSC/NPC lineage plasticity in situ. In contrast to the findings regarding demyelination in the corpus callosum, inducing focal demyelination in the internal capsule did not induce either microglial activation or OPC generation in the SVZ. These results suggest that the mechanism of OPC generation in the SVZ after inducing demyelinating lesions could be different across the demyelinated regions. (c) 2018 S. Karger AG, Basel.