Fluoxetine Upregulates Phosphorylated-AKT and Phosphorylated-ERK1/2 Proteins in Neural Stem Cells: Evidence for a Crosstalk between AKT and ERK1/2 Pathways

Fluoxetine is a widely used antidepressant drug which inhibits the reuptake of serotonin in the central nervous system (CNS). Recent studies have shown that fluoxetine can promote neurogenesis and improve the survival rate of neurons. However, whether fluoxetine modulates the neuroprotection of neural stem cells (NSCs) needs to be elucidated. In this study, we demonstrated that 50 μM fluoxetine significantly upregulated expression of the phosphorylated-AKT and ERK1/2 proteins in NSCs derived from rats. Besides, expression of phosphorylated-AKT and phosphorylated-ERK1/2 in fluoxetine-treated NSCs was effectively blocked (P < 0.05) by both PI3-K inhibitor (LY294002) and MEK inhibitor (PD98059). It was, therefore, concluded that the crosstalk between PI3K/AKT and MAPK/ERK pathways involved AKT and ERK1/2 phosphorylation by fluoxetine treatment. This study points to a novel role of fluoxetine in neuroprotection as an antidepressant drug and also unravels the crosstalk mechanism between the two signaling pathways.

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