Role of the angiogenic factor angiopoietin-1 in the SVZ stem cell niche
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1
University of Coimbra, Center for Neuroscience and Cell Biology, Portugal
In the adult mammalian brain, the subventricular zone (SVZ) hosts stem cells constantly giving rise to new neurons. The vasculature is a major component of the stem cell niches. Indeed, interplay between stem and endothelial cells, via cell-to-cell contacts or endothelial-derived soluble factors, regulates neural stem cell homeostasis and neurogenesis. Even though the effect of endothelial-derived factors is beginning to be unravelled, little is still known about the effect of angiogenic factors on neurogenesis.
In the present work, we propose to examine the effect of the angiogenic factor Angiopoietin-1 (Ang-1) on SVZ neurogenesis.
SVZ cell cultures were performed from neonatal P1–3 C57BL/6 mice. SVZ cells express both Ang-1 and its receptor Tie-2. The system Ang-1/Tie-2 is present in immature cells (Nestin and/or Sox2 positive) and upon differentiation it remains in DCX, GFAP, NG2, MAP-2 and Tau positive cells.
To disclose whether Ang-1 modulates neurogenesis, SVZ cells were incubated 48 h in the presence of 0.5 μg/ml Ang-1. Using Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL), apoptotic nuclei were stained and counted. Ang-1 did not affect apoptotic cell death. To test whether Ang-1 modulates proliferation, SVZ cells were incubated 48 h in the presence of 0.5 μg/ml Ang-1 and exposed to 10 μM BrdU, a thymidine analogue that is incorporated in replicating DNA, 4 h before fixation. Presence of BrdU, as an indicator of cell proliferation, was revealed by immunocytochemistry. Cell counting showed that 0.5 μg/ml Ang-1 increased proliferation in SVZ cells. This effect is mediated by the activation of the Tie-2 receptor as proliferation in cultures exposed to both Ang-1 and the neutralizing anti-Tie-2 antibody was similar to basal levels, i.e found in untreated cultures. SVZ cells were then incubated with 0.5 μg/ml Ang-1 for 7 days to allow differentiation. At the end of the culture session, neuronal differentiation was assessed, both phenotypically through immunorevelation of the neuronal nuclear marker NeuN, and functionally through single cell calcium imaging. Ang-1 increased neuronal differentiation in SVZ cells also via Tie-2 activation.
Disclosing the effects of Ang-1/Tie-2 on SVZ neurogenesis is relevant in the perspective of using SVZ cells in cell-based therapies.
This work is supported by a FCT scholarship, reference SFRH / BD / 32944 / 2006 and PTDC/SAU- NEU/68465/2006.
Conference:
11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009.
Presentation Type:
Poster Presentation
Topic:
Abstracts
Citation:
Rosa
A,
Cortes
L,
Malva
J and
Agasse
F
(2009). Role of the angiogenic factor angiopoietin-1 in the SVZ stem cell niche.
Front. Neurosci.
Conference Abstract:
11th Meeting of the Portuguese Society for Neuroscience.
doi: 10.3389/conf.neuro.01.2009.11.047
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Received:
06 Aug 2009;
Published Online:
06 Aug 2009.
*
Correspondence:
Alexandra Rosa, University of Coimbra, Center for Neuroscience and Cell Biology, Coimbra, Portugal, alexandrarosa@gmail.com