Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai 200040, China.
Molecules. 2011 Dec 6;16(12):10146-56. doi: 10.3390/molecules161210146.
Neurogenesis is a complex process, which contributes to the ability of the adult brain to function normally and adapt to diseases. Epidermal growth factor (EGF) is known to play an important role in neurogenesis; however, the underlying mechanism is still unclear. Here, we hypothesized that brain-derived neurotrophic factor (BDNF) can enhance the effect of EGF on neurogenesis. Using in vitro cell culture of aborted human fetal brain tissues, we investigated proliferation and migration of neural stem/progenitor cells (NSPCs) after treatment with EGF and different concentrations of BDNF. EGF stimulated proliferation and migration of NSPCs, and this effect was significantly enhanced by co-incubation with BDNF. In the NSPCs treated with 50 ng/mL BDNF, BrdU incorporation was significantly increased (from 7.91% to 17.07%), as compared with that in the control. Moreover, the number of migrating cells was at least 2-fold higher than that in the control. Furthermore, phosphorylation of Akt-1 was increased by BDNF treatment, as well. By contrast, the enhancing effect of BDNF on EGF-induced proliferation and migration of NSPCs were abolished by an inhibitor of PI3K, LY294002. These findings suggest that BDNF promotes EGF-induced proliferation and migration of NSPC through the PI3K/Akt pathway, providing significant insights into not only the mechanism underlying EGF-induced neurogenesis but also potential neuronal replacement strategies to treat brain damage.
神经发生是一个复杂的过程，它有助于大脑发挥正常功能并适应疾病。表皮生长因子 (EGF) 被认为在神经发生中发挥着重要作用；然而，其潜在机制仍不清楚。在这里，我们假设脑源性神经营养因子 (BDNF) 可以增强 EGF 对神经发生的作用。我们通过体外培养流产的人胎脑组织，研究了 EGF 和不同浓度的 BDNF 处理后神经干细胞/祖细胞 (NSPCs) 的增殖和迁移。EGF 刺激 NSPCs 的增殖和迁移，而与 BDNF 共孵育则显著增强了这种作用。在 50ng/mlBDNF 处理的 NSPCs 中，BrdU 掺入明显增加（从 7.91%增加到 17.07%），与对照组相比。此外，迁移细胞的数量至少是对照组的 2 倍。此外，BDNF 处理还增加了 Akt-1 的磷酸化。相比之下，PI3K 抑制剂 LY294002 可消除 BDNF 对 EGF 诱导的 NSPC 增殖和迁移的增强作用。这些发现表明，BDNF 通过 PI3K/Akt 通路促进 EGF 诱导的 NSPC 增殖和迁移，不仅为 EGF 诱导的神经发生机制提供了重要见解，而且为治疗脑损伤的潜在神经元替代策略提供了重要见解。
