Levetiracetam (LEV) is a broad-spectrum antiepileptic drug with neuroprotective properties and novel mechanisms of action. Some evidence suggests that LEV may impact adult neurogenesis, but the results are controversial. The present study was aimed to evaluate the effects of LEV on the proliferation and differentiation of rat embryonic neural stem cells (NSCs) and to explore the role of GABA or NMDA receptors. NSCs were isolated from rat fetal ganglionic eminence at embryonic day 14.5. The effects of LEV on viability, proliferation, neurosphere formation, and neuronal or astroglial differentiation of NSCs were assessed using resazurin, BrdU incorporation, immunocytochemistry, quantitative real-time PCR, and western blotting. Additionally, we addressed the relationship between treatment with NMDA and GABA receptor antagonists (MK801 and saclofen, respectively) in combination with LEV on these parameters. The data showed that LEV (50 μM) significantly increased the number ( < 0.01) and diameter of neurospheres ( < 0.05), enhanced proliferation ( < 0.01), and promoted neuronal differentiation, as revealed by significantly increased expressions of DCX and NeuN. The expressions of astroglial markers, GFAP and Olig2, were markedly reduced. The addition of MK801 (10 μM) significantly diminished neurospheres growth ( < 0.001), decreased the number of proliferating cells ( < 0.01), and reduced the number of new neurons ( < 0.001) but increased the astroglial cells ( < 0.001) induced by LEV. Co-treatment with saclofen (25 μM) did not significantly affect LEV-induced NSCs proliferation and differentiation. Our findings suggest that LEV may enhance rat embryonic neurogenesis mainly through an NMDA receptor-mediated mechanism.

中文翻译：

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左乙拉西坦通过 NMDA 受体介导的体外机制促进大鼠胚胎神经发生


左乙拉西坦 (LEV) 是一种广谱抗癫痫药，具有神经保护特性和新颖的作用机制。一些证据表明 LEV 可能会影响成人神经发生，但结果存在争议。本研究旨在评估LEV对大鼠胚胎神经干细胞（NSC）增殖和分化的影响，并探讨GABA或NMDA受体的作用。 NSCs 在胚胎第 14.5 天从大鼠胎儿神经节隆起分离。使用刃天青、BrdU 掺入、免疫细胞化学、定量实时 PCR 和蛋白质印迹评估 LEV 对 NSC 的活力、增殖、神经球形成以及神经元或星形胶质细胞分化的影响。此外，我们还探讨了 NMDA 和 GABA 受体拮抗剂（分别为 MK801 和沙氯芬）联合 LEV 治疗与这些参数之间的关系。数据显示，LEV (50 μM) 显着增加神经球的数量 ( < 0.01) 和直径 ( < 0.05)，增强增殖 ( < 0.01)，并促进神经元分化，DCX 和 NeuN 表达显着增加表明。星形胶质细胞标记物 GFAP 和 Olig2 的表达显着降低。添加 MK801 (10 μM) 显着减少神经球生长 (< 0.001)，减少增殖细胞数量 (< 0.01)，并减少新神经元数量 (< 0.001)，但增加星形胶质细胞 (< 0.001) 诱导的星形胶质细胞 (< 0.001)。水平。与沙氯芬 (25 μM) 共同治疗并没有显着影响 LEV 诱导的 NSC 增殖和分化。我们的研究结果表明，LEV 可能主要通过 NMDA 受体介导的机制增强大鼠胚胎神经发生。