Deficiency of the clock gene Bmal1 affects neural progenitor cell migration
Deficiency of the clock gene Bmal1 affects neural progenitor cell migration
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DOI：
10.1007/s00429-018-1775-1
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发表时间：
2019-01-01
影响因子：
3.1
通讯作者：
von Gall, Charlotte
中科院分区：
文献类型：
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作者：
Ali, Amira A. H.;Schwarz-Herzke, Beryl;von Gall, Charlotte
我们证明了在Bmal 1缺陷（Bmal 1（-/-））小鼠的神经祖细胞（NPC）迁移的分子钟中断的影响。在Bmal 1（-/-）小鼠中，吻侧迁移流（RMS）中的NPC增殖减少，这与我们早期对海马中成年神经发生的研究一致。然而，与野生型同窝小鼠（Bmal 1（+/+）小鼠）相比，Bmal 1（-/-）小鼠的NPC数量显著更高，表明Bmal 1（-/-）小鼠的迁移速度更高。在Bmal 1（-/-）小鼠分离的NPCs中，不仅参与活性氧解毒的基因的迁移速度和表达模式受到影响，而且过氧化氢酶的RNA氧化增加，过氧化氢酶蛋白水平降低。Bmal 1（+/+）迁移表型可以通过过氧化氢酶处理来恢复，而用过氧化氢处理Bmal 1（+/+）小鼠的NPC可以模拟Bmal 1（-/-）迁移表型。因此，我们得出结论，Bmal 1缺乏影响鼻咽癌迁移的结果失调的解毒活性氧。
We demonstrate the impact of a disrupted molecular clock in Bmal1-deficient (Bmal1(-/-)) mice on migration of neural progenitor cells (NPCs). Proliferation of NPCs in rostral migratory stream (RMS) was reduced in Bmal1(-/-) mice, consistent with our earlier studies on adult neurogenesis in hippocampus. However, a significantly higher number of NPCs from Bmal1(-/-) mice reached the olfactory bulb as compared to wild-type littermates (Bmal1(+/+) mice), indicating a higher migration velocity in Bmal1(-/-) mice. In isolated NPCs from Bmal1(-/-) mice, not only migration velocity and expression pattern of genes involved in detoxification of reactive oxygen species were affected, but also RNA oxidation of catalase was increased and catalase protein levels were decreased. Bmal1(+/+) migration phenotype could be restored by treatment with catalase, while treatment of NPCs from Bmal1(+/+) mice with hydrogen peroxide mimicked Bmal1(-/-) migration phenotype. Thus, we conclude that Bmal1 deficiency affects NPC migration as a consequence of dysregulated detoxification of reactive oxygen species.