Abraham Shahar

Endothelial Trophic Support of Neuronal Production and Recruitment from the Adult Mammalian Subependyma

Vascular endothelial cells are among the first cells that ventricular zone neuroblasts encounter during early development. The ventricular zone cells promote angiogenesis by the invading vasculature, with the release of endothelial mitogens. Yet the feedback support of young neurons by endothelial cells (ECs) has not hitherto been explored. We therefore asked whether ECs might participate in neuronal recruitment, by providing neurotrophic support to newly generated neurons. We used the neurogenic subependymal zone (SZ) of the adult rat forebrain as a model system, because of its well-characterized and relatively homogeneous population of neuronal precursor cells. We found that explants of the adult rat SZ raised on ECs generated more neurons, which survived longer, than explants raised on astrocytes, fibroblasts, or laminin. This endothelial trophic effect was humoral, in that it was also noted in SZ explants raised in noncontiguous coculture with ECs grown on porous inserts. RT-PCR for neurotrophin family members revealed that cultures of both human brain- and umbilical cord-derived ECs produced brain-derived neurotrophic factor (BDNF) mRNA, but no detectable NGF, NT-3, or NT-4 mRNA. ELISA revealed that BDNF protein was secreted by ECs into the medium at >1 ng/ml. The neurotrophic effect of ECs could be replaced by added BDNF, and was blocked by addition of 5 microg/ml trkB-Fc to endothelial-SZ cocultures. Thus, endothelial cells can act as sources of secreted BDNF, through which the capillary microvasculature may act to support neuronal recruitment and survival in the CNS.

Neural Precursors and Neuronal Production in the Adult Mammalian Forebraina

bDepartments of Neurology and Neuroscience, and Medicin& and Surgery (Neurosurgery) Cornell University Medical College New York, New York 10021 lDepartments of Cell Biology and Neurosurgery New York Medical College Valhalla, New York I0590 /Department of Neurosurgery Columbia-Presbyterian Medical Center New York, New York 10029 RAitken Neuroscience Center New York, New York 10021 hDepartment of Virology Israel Biological Institute Nes-Ziona, Israel CATHERINE HARRISON-RESTELLI: JINWEN JIANG: