September 3, 2002 | Kunlin Jin, Yonghua Zhu, Yunjuan Sun, Xiao Ou Mao, Lin Xie, and David A. Greenberg*
The study investigates the neurogenic effects of vascular endothelial growth factor (VEGF) in both in vitro and in vivo models. In vitro, VEGF (≥10 ng/ml) increased BrdUrd incorporation into cells expressing immature neuronal markers and increased cell number by 20–30%. This effect was mediated through VEGFR2/Flk-1 receptors, as shown by the use of the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor SU1498. In vivo, intracerebroventricular administration of VEGF increased BrdUrd labeling in the subventricular zone (SVZ) and subgranular zone (SGZ) of the hippocampal dentate gyrus, where VEGFR2/Flk-1 colocalized with the immature neuronal marker doublecortin (Dcx). The increase in BrdUrd labeling was due to increased cell proliferation rather than decreased cell death, as VEGF did not reduce caspase-3 cleavage. Cells labeled with BrdUrd after VEGF treatment included immature and mature neurons, astroglia, and endothelial cells. These findings suggest that VEGF, originally known for its angiogenic and neuroprotective effects, also plays a role in neurogenesis.The study investigates the neurogenic effects of vascular endothelial growth factor (VEGF) in both in vitro and in vivo models. In vitro, VEGF (≥10 ng/ml) increased BrdUrd incorporation into cells expressing immature neuronal markers and increased cell number by 20–30%. This effect was mediated through VEGFR2/Flk-1 receptors, as shown by the use of the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor SU1498. In vivo, intracerebroventricular administration of VEGF increased BrdUrd labeling in the subventricular zone (SVZ) and subgranular zone (SGZ) of the hippocampal dentate gyrus, where VEGFR2/Flk-1 colocalized with the immature neuronal marker doublecortin (Dcx). The increase in BrdUrd labeling was due to increased cell proliferation rather than decreased cell death, as VEGF did not reduce caspase-3 cleavage. Cells labeled with BrdUrd after VEGF treatment included immature and mature neurons, astroglia, and endothelial cells. These findings suggest that VEGF, originally known for its angiogenic and neuroprotective effects, also plays a role in neurogenesis.