PMID- 10383830
OWN - NLM
STAT- MEDLINE
DCOM- 19990928
LR  - 20181201
IS  - 1044-7431 (Print)
IS  - 1044-7431 (Linking)
VI  - 13
IP  - 6
DP  - 1999 Jun
TI  - Endothelial trophic support of neuronal production and recruitment from the adult 
      mammalian subependyma.
PG  - 450-64
AB  - 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.
CI  - Copyright 1999 Academic Press.
FAU - Leventhal, C
AU  - Leventhal C
AD  - Department of Neurology and Neuroscience, Cornell University Medical College, New 
      York, New York 10021, USA.
FAU - Rafii, S
AU  - Rafii S
FAU - Rafii, D
AU  - Rafii D
FAU - Shahar, A
AU  - Shahar A
FAU - Goldman, S A
AU  - Goldman SA
LA  - eng
GR  - R01NS29813/NS/NINDS NIH HHS/United States
GR  - R01NS33106/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Ciliary Neurotrophic Factor)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/antagonists & 
      inhibitors/biosynthesis/metabolism
MH  - Cell Differentiation/drug effects/physiology
MH  - Cell Movement/drug effects/physiology
MH  - Cell Survival/drug effects/physiology
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Culture Media, Conditioned/pharmacology
MH  - Endothelium, Vascular/*cytology/metabolism
MH  - Ependyma/*cytology
MH  - Extracellular Space/metabolism
MH  - Neurons/*cytology/drug effects
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor Protein-Tyrosine Kinases/physiology
MH  - Receptor, Ciliary Neurotrophic Factor
MH  - Receptors, Nerve Growth Factor/physiology
MH  - Recombinant Fusion Proteins/pharmacology
EDAT- 1999/06/29 00:00
MHDA- 1999/06/29 00:01
CRDT- 1999/06/29 00:00
PHST- 1999/06/29 00:00 [pubmed]
PHST- 1999/06/29 00:01 [medline]
PHST- 1999/06/29 00:00 [entrez]
AID - S1044-7431(99)90762-5 [pii]
AID - 10.1006/mcne.1999.0762 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 1999 Jun;13(6):450-64. doi: 10.1006/mcne.1999.0762.