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Effects of taxol on neuronal differentiation of postnatal neural stem cells cultured from mouse subventricular zone
Differentiation ( IF 2.9 ) Pub Date : 2021-04-08 , DOI: 10.1016/j.diff.2021.03.001
Ki-Youb Park 1 , Seokyung Kim 1 , Man Su Kim 2
Affiliation  

Taxol (paclitaxel), a chemotherapeutic agent for several cancers, can adversely affect the peripheral nervous system. Recently, its negative impact on cognitive function in cancer patients has become evident. In rodents, taxol impaired learning and memory, with other possible negative effects on the brain. In this study, we investigated the effects of taxol on cultured neural stem cells (NSCs) from the mouse neurogenic region, the subventricular zone (SVZ). Taxol significantly decreased both proliferation and neuronal differentiation of NSCs. Transient treatment with taxol for one day during a 4-day differentiation greatly decreased neurogenesis along with an abnormal cell cycle progression. Yet, taxol did not kill differentiated Tuj1+ neurons and those neurons had longer neurites than neurons under control conditions. For glial differentiation, taxol significantly reduced oligodendrogenesis as observed by immunostaining for Olig2 and O4. However, differentiation of astrocytes was not affected by taxol. In contrast, differentiated oligodendrocytes were extremely sensitive to taxol. Almost no Olig2-positive cells were observed after three days of treatment with taxol. Taxol has distinct effects on neurons and glial cells during their production through differentiation from NSCs as well as post-differentiation. Thus, we suggest that taxol might interfere with neurogenesis of NSCs possibly through a disturbance in the cell cycle and may eliminate differentiated oligodendrocytes.



中文翻译:

紫杉醇对小鼠脑室下区培养的出生后神经干细胞神经元分化的影响

紫杉醇(紫杉醇)是多种癌症的化学治疗剂,会对周围神经系统产生不利影响。最近,它对癌症患者认知功能的负面影响变得明显。在啮齿动物中,紫杉醇会损害学习和记忆,并对大脑产生其他可能的负面影响。在这项研究中,我们研究了紫杉醇对来自小鼠神经源性区域脑室下区 (SVZ) 的培养神经干细胞 (NSC) 的影响。紫杉醇显着降低了神经干细胞的增殖和神经元分化。在为期 4 天的分化过程中,用紫杉醇短暂治疗 1 天大大减少了神经发生以及异常的细胞周期进程。然而,紫杉醇并没有杀死分化的 Tuj1+ 神经元,而且这些神经元的神经突比对照条件下的神经元长。对于胶质细胞分化,通过 Olig2 和 O4 的免疫染色观察到,紫杉醇显着减少了少突胶质细胞生成。然而,星形胶质细胞的分化不受紫杉醇的影响。相比之下,分化的少突胶质细胞对紫杉醇极为敏感。用紫杉醇处理三天后几乎没有观察到 Olig2 阳性细胞。紫杉醇在神经元和神经胶质细胞的生产过程中通过从 NSC 分化和分化后对它们产生不同的影响。因此,我们认为紫杉醇可能通过扰乱细胞周期来干扰 NSCs 的神经发生,并可能消除分化的少突胶质细胞。分化的少突胶质细胞对紫杉醇极为敏感。用紫杉醇处理三天后几乎没有观察到 Olig2 阳性细胞。紫杉醇在神经元和神经胶质细胞的生产过程中通过从 NSC 分化和分化后对它们产生不同的影响。因此,我们认为紫杉醇可能通过扰乱细胞周期来干扰 NSCs 的神经发生,并可能消除分化的少突胶质细胞。分化的少突胶质细胞对紫杉醇极为敏感。用紫杉醇处理三天后几乎没有观察到 Olig2 阳性细胞。紫杉醇在神经元和神经胶质细胞的生产过程中通过从 NSC 分化和分化后对它们产生不同的影响。因此,我们认为紫杉醇可能通过扰乱细胞周期来干扰 NSCs 的神经发生,并可能消除分化的少突胶质细胞。

更新日期:2021-04-11
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