Document Detail

GABA(A) Receptor Signaling Induces Osmotic Swelling and Cell Cycle Activation of Neonatal Prominin(+) Precursors.
MedLine Citation:
PMID:  21732488     Owner:  NLM     Status:  In-Data-Review    
Signal-regulated changes in cell size affect cell division and survival and therefore are central to tissue morphogenesis and homeostasis. In this respect, GABA receptors (GABA(A) Rs) are of particular interest because allowing anions flow across the cell membrane modulates the osmolyte flux and the cell volume. Therefore, we have here investigated the hypothesis that GABA may regulate neural stem cell proliferation by inducing cell size changes. We found that, besides neuroblasts, also neural precursors in the neonatal murine subependymal zone sense GABA via GABA(A) Rs. However, unlike in neuroblasts, where it induced depolarization-mediated [Ca(2+) ](i) increase, GABA(A) Rs activation in precursors caused hyperpolarization. This resulted in osmotic swelling and increased surface expression of epidermal growth factor receptors (EGFRs). Furthermore, activation of GABA(A) Rs signaling in vitro in the presence of EGF modified the expression of the cell cycle regulators, phosphatase and tensin homolog and cyclin D1, increasing the pool of cycling precursors without modifying cell cycle length. A similar effect was observed on treatment with diazepam. We also demonstrate that GABA and diazepam responsive precursors represent prominin(+) stem cells. Finally, we show that as in in vitro also in in vivo a short administration of diazepam promotes EGFR expression in prominin(+) stem cells causing activation and cell cycle entry. Thus, our data indicate that endogenous GABA is a part of a regulatory mechanism of size and cell cycle entry of neonatal stem cells. Our results also have potential implications for the therapeutic practices that involve exposure to GABA(A) Rs modulators during neurodevelopment. STEM CELLS 2011;29:307-319.
Tiziana Cesetti; Tatiana Fila; Kirsten Obernier; C Peter Bengtson; Yuting Li; Claudia Mandl; Gabriele Hölzl-Wenig; Francesca Ciccolini
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  29     ISSN:  1549-4918     ISO Abbreviation:  Stem Cells     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-07-06     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  United States    
Other Details:
Languages:  eng     Pagination:  307-19     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 AlphaMed Press.
Department of Neurobiology, Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, Heidelberg, Germany.
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