Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
J Mol Neurosci. 2013 Feb;49(2):244-9. doi: 10.1007/s12031-012-9822-5. Epub 2012 Jun 7.
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.
氟西汀是一种广泛应用于治疗抑郁症的药物，它可以抑制中枢神经系统（CNS）中血清素的再摄取。最近的研究表明，氟西汀可以促进神经发生并提高神经元的存活率。然而，氟西汀是否调节神经干细胞（NSCs）的神经保护作用仍需要阐明。在本研究中，我们证明了 50μM 的氟西汀可以显著上调大鼠来源的 NSCs 中磷酸化-AKT 和 ERK1/2 蛋白的表达。此外，PI3-K 抑制剂（LY294002）和 MEK 抑制剂（PD98059）可以有效阻断（P<0.05）氟西汀处理的 NSCs 中磷酸化-AKT 和磷酸化-ERK1/2 的表达。因此，我们得出结论，PI3K/AKT 和 MAPK/ERK 通路之间的串扰通过氟西汀处理来参与 AKT 和 ERK1/2 的磷酸化。本研究指出了氟西汀作为抗抑郁药在神经保护中的新作用，并揭示了这两条信号通路之间的串扰机制。
