Effect and mechanism of lithium on the differentiation of neural stem cells

English Keywords:Lithium  Neural stem cells  Differentiation

English Abstract:

  【Abstract】 Objectives: To investigate the effect and its underlying mechanism of lithium on modulating neural stem cells differentiation. Methods: NSCs were isolated from the subventricular zone of neonatal Fischer 344 Rat. The growth curve of differentiating NSCs was detected by using Cyquant assay. Immunocytochemistry staining combining with BrdU incorporation assay were used to detectneuronal marker Tuj1 and astrocytes marker GFAP and S100β, the percentage, as well as the total numbers of each lineage were also estimated. TNUEL apoptosis assay was also performed to rule out the lithium toxicity. Finally, lithium and GSK3β inhibitor-SB216763′s effect on regulating neuraonal and astrocytes were tested and compared. Results: Lithium concentration lower than 3mM was non-toxic in differentiating NSCs. 1mM lithium stimulated neuronal production by 1.47±0.06 folds(P<0.05), while SB216763 increased by 2.25±0.07 folds(P<0.05), 3mM lithium reduced GFAP+ cell number to 0.55±0.02 folds(P<0.05) compared with control group, S100β staning result showed the similar tendency, conversely, SB216763 did not reduce GFAP+ cell number, with 0.90±0.06 folds compared with control group(P>0.05). Conclusions: Lithium exerts dual roles on NSCs′s differentiation. It stimulates neurogenesis at concentration of 1mM with its inhibition on doumregulating GSK3β pathway, meanwhile suppresses astrogliogenesis at concentration of 3mM, which may be mediated by non-canonical pathway.