Taurine Effect on Stem Cells and Synaptogenesis Figure 3. Effects of taurine treatment on cell proliferation in the dentate gyrus of cultured hippocampal slices. EdU labeling was used to assess cell proliferation. The culture medium was changed to serum free condition on day 7 and taurine was added to the medium on day 9. EdU (10 mM) was added to the culture medium at day 11 and the slices were fixed and processed for EdU staining on day 17. Numbers of EdU positive cells in dentate gyrus were analyzed and the data are presented as mean 6 SEM. (* P,0.05) (A). Images showing EdU-labeled cells in the dentate gyrus of control (upper panel) and taurine treated groups (lower panel) (B). SGZ and GCL denote subgranular zone and granule cell layer respectively. Scale bar = 20 mm. doi:10.1371/journal.pone.0042935.g003 showed that MAPK is involved in the proliferative effects of taurine in osteocytes [34]. We demonstrated that taurine supplementation increased ERK1/2 phosphorylation, indicating a role of this pathway in taurine induced NPC proliferation. The ERK inhibitor (PD98059) causes significant inhibition of prolif- eration in taurine treated NPCs further supporting that taurine- mediated ERK1/2 phosphorylation increases proliferation of NPCs. Taurine’s proliferative effect on NPC occurs in addition to that of the growth factor effects from the growth media. To the best of our knowledge, this is the first report demonstrating taurine induces proliferation in neural progenitor cells through activating ERK1/2 pathway. Cultured NPCs differentiate under appropriate conditions into neurons and glia [35]. However, taurine did not significantly increase the number of neurons or astrocytes differentiated from NPCS, though a modest 8% increase in the number of neurons was observed in cultures containing taurine. Recently, Herna´ndez- Ben´ıtez et al. [28] also reported that taurine did not change the number of embryonic NPCs differentiated to neurons, but the authors found an increase in NPCs differentiated into astrocytes (GFAP-positive cells). These effects may depend on the age of embryos that the progenitor cells were derived from, as they have used embryonic NPCs instead of the P5 NPCs that we are using in our study, and possibly also dependent on the cell culture conditions [36,37]. PLOS ONE | www.plosone.org 5 August 2012 | Volume 7 | Issue 8 | e42935