Research ReportTemporal changes in the response of SVZ neural stem cells to intraventricular administration of growth factors

- Intraventricularly administered FGF2/EGF induces proliferation of SVZ stem cells.
- Growth factors increase stem cells at the expense of their neuronal differentiation.
- Enhanced neurogenesis occurs only after the termination of growth factor therapy.
- Prolonged growth factor therapy rather attenuates the proliferation of stem cells.
- Optimizing the duration of treatment is important for enhancement of neurogenesis.

In vivo growth factor (GF) treatment is a promising approach to enhance the regenerative capacity of neural stem cells (NSCs) for brain repair. However, how exogenous GFs affect endogenous NSCs is not well understood. This study investigated the impact of intraventricular administration of fibroblast growth factor 2 and epidermal growth factor on NSCs in the subventricular zone of intact adult mice. GFs were administered for various periods (3, 7, 10, and 14 days), and the proliferation and neuronal production of NSCs were assessed during and after GF treatment. We found that proliferation of NSCs and their progeny is markedly augmented during the first 7 days after the initiation of GF treatment. GF treatment for longer periods, however, did not lead to further increases in the NSC pool, but rather attenuated such proliferation and inhibited neurogenesis. As a result, the production of new olfactory bulb neurons was increased in animals treated with GFs for 7 days but decreased in animals treated for 14 days. These results show time-dependent changes in the response of NSCs to exogenous GFs and demonstrate that precise control of the duration of GF treatment is important for significant enhancement of neuronal production by NSCs in vivo for brain repair.