Adult neural stem and progenitor cells (NSPCs) reside in the dentate gyrus (DG) of the hippocampus throughout the lifespan of most mammalian species. In addition to generating new neurons, NSPCs may alter their niche via secretion of growth factors and cytokines. We recently showed that adult DG NSPCs secrete vascular endothelial growth factor (VEGF), which is critical for maintaining adult neurogenesis. Here, we asked whether NSPC-derived VEGF alters hippocampal function independent of adult neurogenesis. We found that loss of NSPC-derived VEGF acutely impaired hippocampal memory, caused neuronal hyperexcitability and exacerbated excitotoxic injury. Conversely, we observed that overexpression of VEGF reduced microglial response to excitotoxic injury. We also found that NSPCs generate substantial proportions of total DG VEGF and VEGF disperses widely throughout the DG, both of which help explain how this anatomically-restricted cell population could modulate function broadly. These findings suggest that NSPCs actively support and protect DG function via secreted VEGF, thereby providing a non-neurogenic functional dimension to endogenous NSPCs.

成体神经干细胞和祖细胞 （NSPC） 在大多数哺乳动物物种的整个生命周期中都存在于海马体的齿状回 （DG） 中。除了产生新的神经元外，NSPC 还可以通过分泌生长因子和细胞因子来改变其生态位。我们最近表明，成体 DG NSPC 分泌血管内皮生长因子 （VEGF），这对于维持成体神经发生至关重要。在这里，我们询问了 NSPC 衍生的 VEGF 是否独立于成体神经发生改变海马功能。我们发现 NSPC 衍生的 VEGF 丢失急性损害了海马记忆，导致神经元过度兴奋并加剧了兴奋性毒性损伤。相反，我们观察到 VEGF 的过表达降低了小胶质细胞对兴奋性毒性损伤的反应。我们还发现，NSPC 产生相当大比例的总 DG VEGF，并且 VEGF 广泛分散在整个 DG 中，这两者都有助于解释这种解剖学限制性细胞群如何广泛调节功能。这些发现表明，NSPCs 通过分泌的 VEGF 积极支持和保护 DG 功能，从而为内源性 NSPC 提供非神经源性功能维度。