Melatonin promotes proliferation of neural stem cells from adult mouse spinal cord via the PI3K/AKT signaling pathway.

In this study, we tested the effect of melatonin on proliferation and differentiation of neural stem/progenitor cells (NSPCs) obtained from adult mouse spinal cord. We found that melatonin increases neurosphere formation from adult spinal cord NSPCs but does not alter the differentiation of the cells. Western blot results show that adult spinal cord NSPCs express both MT1 and MT2 melatonin receptors. The melatonin receptor antagonist 4P-PDOT abrogates the melatonin-induced neurosphere formation. Melatonin increases the phosphorylation level of protein kinase B (AKT). Blockage of phosphatidylinositol 3-kinase (PI3K), a kinase upstream of AKT, abolishes the stimulatory effect of melatonin on spinal cord NSPCs. We conclude that melatonin promotes the proliferation of adult spinal cord NSPCs via the PI3K/AKT signaling pathway.