Disrupted migration and proliferation of neuroblasts after postnatal administration of angiogenesis inhibitor

In adult rodents, neuroblasts originating from the subventricular zone migrate tangentially through the rostral migratory stream (RMS) toward the olfactory bulb where they differentiate into interneurons. Neuroblasts in the RMS migrate in chains for a long distance along specifically arranged blood vessels which promote their migration. Although blood vessels in the neurogenic region of the forebrain are present early in development, their rearrangement into this specific pattern takes place during the first postnatal weeks. Here we examined the relevance of this rearrangement to the migration-guiding "scaffold" for the neurogenic processes in the RMS such as cell migration and proliferation. To disturb the reorganization of blood vessels, endostatin - an inhibitor of angiogenesis, was administered systemically to rat pups during the first postnatal week. Ten days or three months later, the arrangement of blood vessels, migration and proliferation of cells in the RMS were assessed. As we expected, the inhibition of angiogenesis disrupted rearrangement of blood vessels in the RMS. The rearrangement's failure resulted in a strong disruption of the mode and direction of neuroblast migration. Chain migration failed and neuroblasts migrated out of the RMS. The inhibition caused a slight increase in the number of proliferating cells in the RMS. The consequences were more obvious ten days after the inhibition of angiogenesis, although they persisted partly into adulthood. Altogether, here we show that the process of rearrangement of blood vessels in the RMS during the early postal period is crucial to ensure the regular course of postnatal neurogenesis.