Ochi Takashi, Nakatomi Hirofumi, Ito Akihiro, Imai Hideaki, Okabe Shigeo, Saito Nobuhito
Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; Department of Cellular Neurobiology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8654, Japan.
Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Brain Res. 2016 Apr 1;1636:118-129. doi: 10.1016/j.brainres.2016.01.046. Epub 2016 Feb 2.
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.
体内生长因子（GF）治疗是一种很有前景的方法，可增强神经干细胞（NSC）的再生能力以修复大脑。然而，外源性生长因子如何影响内源性神经干细胞尚不清楚。本研究调查了在完整成年小鼠脑室下区脑室内给予成纤维细胞生长因子2和表皮生长因子对神经干细胞的影响。生长因子给药不同时长（3、7、10和14天），并在生长因子治疗期间及之后评估神经干细胞的增殖和神经元生成。我们发现，在开始生长因子治疗后的前7天，神经干细胞及其子代的增殖显著增加。然而，更长时间的生长因子治疗并未导致神经干细胞库进一步增加，反而减弱了这种增殖并抑制了神经发生。结果，接受生长因子治疗7天的动物中新的嗅球神经元生成增加，但接受治疗14天的动物中则减少。这些结果显示了神经干细胞对外源性生长因子反应的时间依赖性变化，并表明精确控制生长因子治疗的持续时间对于在体内显著增强神经干细胞用于大脑修复的神经元生成非常重要。
