Wang Zhuyao, Wang Juan, Li Jingjin, Wang Xiaohui, Yao Yuzhen, Zhang Xiaojin, Li Chuanfu, Cheng Yunlin, Ding Guoxian, Liu Li, Ding Zhengnian
Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Guangzhou Road 300, Nanjing 210029, China.
Int J Dev Neurosci. 2011 Jun;29(4):415-22. doi: 10.1016/j.ijdevneu.2011.03.001. Epub 2011 Mar 21.
Lithium, a drug used for the treatment of bipolar disorder, has been shown to affect different aspects of neuronal development such as neuritogenesis, neurogenesis and survival. The underlying mechanism responsible for lithium's influence on neuronal development, however, still remains to be elucidated. In the present study, we demonstrate that lithium increases the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt) and promotes neurite outgrowth in mouse N2a neuroblastoma cells (N2a). The inactivation of mitogen-activated protein kinase kinase (MEK)/ERKs signaling with a MEK inhibitor inhibits neurite outgrowth, but it enhances Akt activation in lithium-treated N2a cells. Furthermore, the inactivation of phosphoinositide-3-kinase (PI3K)/Akt signaling with a PI3K inhibitor increases both lithium-induced ERKs activation and lithium-induced neurite outgrowth. Taken together, our study suggests that lithium-induced neurite outgrowth in N2a cells is regulated by cross-talk between the MEK/ERKs and PI3K/Akt pathways and requires the activation of the MEK/ERKs signaling.
锂是一种用于治疗双相情感障碍的药物，已被证明会影响神经元发育的不同方面，如神经突生成、神经发生和存活。然而，锂对神经元发育影响的潜在机制仍有待阐明。在本研究中，我们证明锂可增加细胞外信号调节激酶（ERK）和蛋白激酶B（Akt）的磷酸化，并促进小鼠N2a神经母细胞瘤细胞（N2a）的神经突生长。用MEK抑制剂使丝裂原活化蛋白激酶激酶（MEK）/ERK信号失活可抑制神经突生长，但可增强锂处理的N2a细胞中的Akt活化。此外，用PI3K抑制剂使磷酸肌醇-3-激酶（PI3K）/Akt信号失活可增加锂诱导的ERK活化和锂诱导的神经突生长。综上所述，我们的研究表明，锂诱导的N2a细胞神经突生长受MEK/ERK和PI3K/Akt途径之间的相互作用调节，并且需要MEK/ERK信号的激活。
