Naruse Masae, Shibasaki Koji, Shimauchi-Ohtaki Hiroya, Ishizaki Yasuki
Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Japan.
Dev Neurosci. 2018;40(1):54-63. doi: 10.1159/000486332. Epub 2018 Jan 25.
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.
在正常生理条件下，源自脑室下区（SVZ）神经干细胞（NSCs）的神经母细胞沿着头端迁移流迁移至嗅球，以生成中间神经元。当发生脱髓鞘时，SVZ中的神经干细胞或神经祖细胞（NPCs）会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谱系的可塑性可能倾向于少突胶质细胞生成。然而，其机制仍不清楚。本研究表明，胼胝体的局灶性脱髓鞘不仅会导致脱髓鞘部位的小胶质细胞活化，还会导致SVZ中的小胶质细胞活化，并显著增加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会减少SVZ中OPC的生成，这表明胼胝体局灶性脱髓鞘诱导的SVZ中小胶质细胞活化在原位调节NSC/NPC谱系可塑性。与胼胝体脱髓鞘的研究结果相反，在内囊诱导局灶性脱髓鞘不会诱导SVZ中的小胶质细胞活化或OPC生成。这些结果表明，诱导脱髓鞘病变后SVZ中OPC生成的机制在不同的脱髓鞘区域可能有所不同。
