Glycogen Synthase Kinase 3ß (GSK3ß) is a multifunctional enzyme involved in cell metabolism, apoptosis signaling, cytoskeletal rearrangement, transcriptional regulation, and developmental molecular pathways. In the present study, we inhibited GSK3ß in neurosphere cultures isolated from the subventricular zone of the adult rat brain by the specific low-molecular weight inhibitor SB216763 and analyzed changes in protein expression on a proteomic scale. Whole cell lysates of neurospheres differentiated in vitro by removal of growth factors and in the presence of the inhibitor were subjected to two-dimensional gel electrophoresis and compared to non-inhibited cultures. We identified changes in protein expression in energy metabolism, cytoskeletal rearrangement, protein folding, cellular survival and neuronal differentiation. In some of the genes encoding for the differentially expressed proteins, we found the binding sequence for GSK3ß-dependent transcription factors, providing further evidence of their transcriptional regulation by GSK3ß. In conclusion, GSK3ß is a key player in regulating differentiation and proliferation in adult neuronal stem cells.

Support: German Ministry of Education and Research (BMBF, NGFN-2).