Leptin and its intracellular signaling pathway maintains the neurosphere

Leptin is associated with the maintenance of epidermal growth factor (EGF)-reactive neural lineage cells, including the neural progenitors. One-day treatment with leptin (10, 100, or 1000 ng/ml) followed by EGF treatment increased the number of small-sized and mid-sized colonies compared with the nonleptin treatment. Leptin prevented the inactivation of the phosphatidylinositol 3-kinase (PI3 K) and extracellular signal regulated kinase (ERK) pathways in neurosphere cells cultured in the non-EGF medium. Bromodeoxyuridine (BrdU) incorporation into the neurosphere cells induced by leptin was suppressed by LY294002, a PI3 K inhibitor, but not by U0126, a MEK1/2 inhibitor, which activates ERK1/2, although U0126 decreased phosphorylated extracellular signal regulated kinase levels. These results suggest that leptin maintains the self-renewal ability and EGF reactivity of immature neural lineage cells and the signal is mediated, at least in part, by the PI3 K pathway.