Abstract
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.
Highlights
Neurogenesis is a complex developmental process involving proliferation, differentiation, migration, survival, maturation and functional integration of neural stem/progenitor cells (NSPCs) into neuronal circuits [1]
We investigated the effect of brain-derived neurotrophic factor (BDNF) on the Epidermal growth factor (EGF)-induced NSPCs proliferation and migration by using an in vitro human fetal brain cell culture system
These results were coincident with those obtained from Western blotting analysis of phosphorylation of Akt-1 (Figure 2). These results suggested that the PI3K/Akt pathway is involved in BDNF stimulation of EGF-induced proliferation and migration of NSPCs
Summary
Neurogenesis is a complex developmental process involving proliferation, differentiation, migration, survival, maturation and functional integration of neural stem/progenitor cells (NSPCs) into neuronal circuits [1]. Epidermal growth factor (EGF) regulates cell growth by stimulating proliferation and migration of different types of cells. In the central nervous system (CNS), EGF mRNA has been detected in many regions, including the brainstem, cerebellum, cerebral cortex, hippocampus, olfactory bulb, and striatum. EGF has been demonstrated to increase the number of newborn cells in the striatum either by stimulating migration of SVZ cells or by promoting proliferation of local progenitor cells [6]. EGF has beenshown to stimulate the migration and proliferation of murine progenitor cells in vivo after transplantation to the adult rat brain [8]. EGF and its associated signaling pathways during human neurogenesis remain unclear
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