Marta Boccazzi and Chiara Rolando contributed equally to this work.
Purines regulate adult brain subventricular zone cell functions: Contribution of reactive astrocytes
Version of Record online: 31 DEC 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 62, Issue 3, pages 428–439, March 2014
How to Cite
Boccazzi, M., Rolando, C., Abbracchio, M. P., Buffo, A. and Ceruti, S. (2014), Purines regulate adult brain subventricular zone cell functions: Contribution of reactive astrocytes. Glia, 62: 428–439. doi: 10.1002/glia.22614
Maria P. Abbracchio, Annalisa Buffo, and Stefania Ceruti contributed equally to this work.
- Issue online: 20 JAN 2014
- Version of Record online: 31 DEC 2013
- Manuscript Accepted: 21 NOV 2013
- Manuscript Revised: 19 NOV 2013
- Manuscript Received: 26 SEP 2013
- Italian Ministry of Health . Grant Number: RF-CCM-2008-1248388
- Compagnia di San Paolo, Project GLIAREP 2008
- P2Y1 receptor;
- neurogenic niche;
- adult neurogenesis
Brain injuries modulate activation of neural stem cells (NSCs) in the adult brain. In pathological conditions, the concentrations of extracellular nucleotides (eNTs) raise several folds, contribute to reactive gliosis, and possibly directly affect subventricular zone (SVZ) cell functioning. Among eNTs and derived metabolites, the P2Y1 receptor agonist ADP strongly promotes astrogliosis and might also influence SVZ progenitor activity. Here, we tested the ability of the stable P2Y1 agonist adenosine 5′-O-(2-thiodiphosphate) (ADPβS) to control adult NSC functions both in vitro and in vivo, with a focus on the possible effects exerted by reactive astrocytes. In the absence of growth factors, ADPβS promoted proliferation and differentiation of SVZ progenitors. Moreover, ADPβS-activated astrocytes markedly changed the pattern of released cytokines and chemokines, and strongly modulated neurosphere-forming capacity of SVZ progenitors. Notably, a significant enhancement in proliferation was observed when SVZ cells, initially grown in the supernatant of astrocytes exposed to ADPβS, were shifted to normal medium. In vivo, ADPβS administration in the lateral ventricle of adult mice by osmotic minipumps caused diffused reactive astrogliosis, and a strong response of SVZ progenitors. Indeed, proliferation of glial fibrillary acidic protein-positive NSCs increased and led to a significant expansion of SVZ transit-amplifying progenitors and neuroblasts. Lineage tracing experiments performed in the GLAST::CreERT2;Rosa-YFP transgenic mice further demonstrated that ADPβS promoted proliferation of glutamate/aspartate transporter-positive progenitors and sustained their progression toward the generation of rapidly dividing progenitors. Altogether, our results show that the purinergic system crucially affects SVZ progenitor activities both directly and through the involvement of reactive astrocytes. GLIA 2014;62:428–439