Knowledge Bank

Adult neurogenesis is the continued process of generating new neurons throughout life. In the mammalian brain, adult neurogenesis occurs in both the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus. Adult neurogenesis in the DG of the hippocampus is thought to play a role in memory and learning systems. The radial glial like neural stem cells (RGL-NSCs) and their progeny intermediate progenitor cells (IPCs) involved in adult hippocampal neurogenesis are surrounded by a microenvironment called the neurogenic niche, a major feature of which is local blood vessels. The vasculature within the niche provides neural stem and progenitor cells (NSPCs) access to oxygen and circulating support molecules such as growth factors. Additionally, blood vessels can act as scaffolding for neuroblasts and progenitors to migrate tangentially. Past research has validated that inside the DG of mice, during adulthood, the vasculature is especially dense and the NSCs, reside in close proximity to local blood vessels. Though the proximity of NSCs to vessels in adulthood has been well established, little is known about when it develops. To characterize the developmental time course of NSPCs proximity to blood vessels, I quantified RGL-NSC and IPC association with blood vessels in wildtype mice at 2, 3, 5, and 9 weeks of age. I used immunofluorescent phenotypic markers to identify RGL-NSCs, IPCs and endothelial cells in fixed tissue sections. I found that there was a progressive reduction in the distance between RGL-NSC bodies and the nearest blood vessel from 2 to 9 weeks of age. These results were similarly true for the distance between IPC bodies and the nearest blood vessel. These results suggest that the association of NSPCs with vasculature is not a preserved feature from early development, but rather one that arises de novo during postnatal maturation. Further, these results imply that the DG neurogenic vascular niche continues to develop postnatally and is not complete until adulthood. To further characterize the development of the vasculature niche, I am currently using a transcardially perfused dye coupled with postmortem tissue clearing of thick brain slices to create 3D rendered images of the DG vasculature network in mice at 2, 3, and 9 weeks of age. These future studies investigating the changing vascular niche alongside the development of the NSCs will provide insight into the unique relationship between NSPCs and vasculature that may aid in the preservation of neurogenesis in the adult DG.