Control of neural stem cell proliferation and lineage progression in the postnatal subventricular zone by GABAergic signaling
Final Report Abstract
We have investigated the contribution of γ-aminobutyric acid type A receptors (GABAArs) to the regulation of neural stem cell (NSC) proliferation in the subependymal zone (SEZ), which represents the main neurogenic niche in the postnatal murine brain. To pursue such a goal we have first measured the characteristics of GABAAr currents in neural precursors and then used a pharmacological approach to modulate GABAergic currents in vitro and in vivo to analyze their effect on NSC proliferation. This analysis revealed that NSCs in the neonatal SEZ NSCs display benzodiazepine sensitive GABAArs and that their activation promotes the overexpression of the epidermal growth factor receptor (Egfr) at the cell membrane and cell cycle entry in vitro and in vivo. The mechanism underlying this effect involves GABAAr-induced hyperpolarization and osmotic swelling of NSCs. We also could show that GABAAr signalling promotes osmotic swelling by affecting Cl- movements as well as the expression of water channel Aqp4 at the cell membrane and that GABAAr signalling also modulates Egfr and Aqp4 expression in the adult SEZ.
Publications
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GABAA receptor signalling induces osmotic swelling and cell cycle activation of neonatal Prominin+ precursors. Stem Cells 2011 29:307-319
Cesetti T, Fila T, Obernier K, Bengtson CP, Li Y, Mandl C, Hölzl-Wenig G, Ciccolini F
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GABA Not Only a Neurotransmitter: Osmotic Regulation by GABA(A)R Signaling. Front Cell Neurosci. 2012 6:3
Cesetti T, Ciccolini F, Li Y
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γ-Aminobutyric A Receptor (GABAAR) Regulates Aquaporin 4 Expression in the Subependymal Zone: relevance to neural precursors and water exchange. February 13, 2015, The Journal of Biological Chemistry, 290, 4343-4355. First Published on December 24, 2014
Li Y, Schmitz-Edelkraut U, Poetz F, Oliva I, Mandl C, Hölzl-Wenig G, Schönig K, Bartsch D, Ciccolini F
