Lu Lu, Zhou Hengxing, Pan Bin, Li Xueying, Fu Zheng, Liu Jun, Shi Zhongju, Chu Tianci, Wei Zhijian, Ning Guangzhi, Feng Shiqing
Department of Orthopaedics, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, 300052, People's Republic of China.
Key Laboratory of Immuno Microenvironment and Disease of the Educational Ministry of China, Department of Immunology, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China.
Neurochem Res. 2017 Apr;42(4):1254-1266. doi: 10.1007/s11064-016-2167-7. Epub 2017 Mar 21.
Valproic acid (VPA), an anticonvulsant and mood-stabilizing drug, can induce neuronal differentiation, promote neurite extension and exert a neuroprotective effect in central nervous system (CNS) injuries; however, comparatively little is known regarding its action on mouse embryonic neural stem cells (NSCs) and the underlying molecular mechanism. Recent studies suggested that c-Jun N-terminal kinase (JNK) is required for neurite outgrowth and neuronal differentiation during neuronal development. In the present study, we cultured mouse embryonic NSCs and treated the cells with 1 mM VPA for up to 7 days. The results indicate that VPA promotes the neuronal differentiation of mouse embryonic NSCs and neurite outgrowth of NSC-derived neurons; moreover, VPA induces the phosphorylation of c-Jun by JNK. In contrast, the specific JNK inhibitor SP600125 decreased the VPA-stimulated increase in neuronal differentiation of mouse embryonic NSCs and neurite outgrowth of NSC-derived neurons. Taken together, these results suggest that VPA promotes neuronal differentiation of mouse embryonic NSCs and neurite outgrowth of NSC-derived neurons. Moreover, JNK activation is involved in the effects of VPA stimulation.
丙戊酸(VPA)是一种抗惊厥和情绪稳定药物,可诱导神经元分化、促进神经突延伸,并对中枢神经系统(CNS)损伤发挥神经保护作用;然而,关于其对小鼠胚胎神经干细胞(NSCs)的作用及潜在分子机制,人们了解相对较少。最近的研究表明,c-Jun氨基末端激酶(JNK)在神经元发育过程中对神经突生长和神经元分化是必需的。在本研究中,我们培养了小鼠胚胎NSCs,并用1 mM VPA处理细胞长达7天。结果表明,VPA促进小鼠胚胎NSCs的神经元分化以及NSC衍生神经元的神经突生长;此外,VPA诱导JNK介导的c-Jun磷酸化。相反,特异性JNK抑制剂SP600125降低了VPA刺激引起的小鼠胚胎NSCs神经元分化增加以及NSC衍生神经元的神经突生长。综上所述,这些结果表明VPA促进小鼠胚胎NSCs神经元分化以及NSC衍生神经元的神经突生长。此外,JNK激活参与了VPA刺激的作用。