c-Jun Amino-Terminal Kinase is Involved in Valproic Acid-Mediated Neuronal Differentiation of Mouse Embryonic NSCs and Neurite Outgrowth of NSC-Derived Neurons

• DOI: 10.1007/s11064-016-2167-7
• Publication Date: 2017-03-21T00:42:58Z
• Authors: Lu Lu; Hengxing Zhou; Bin Pan; Xueying Li; Zheng Fu; Jun Liu; Zhongju Shi; Tianci Chu; Zhijian Wei; Guangzhi Ning; Shiqing Feng
• Keywords: Anthracenes; Neurons; Original Paper; Valproic Acid; Neuronal Outgrowth; JNK Mitogen-Activated Protein Kinases; Cell Differentiation; Biochemistry; 3. Good health; Mice, Inbred C57BL; Cellular and Molecular Neuroscience; Mice; Neural Stem Cells; Animals; Cells, Cultured; Embryonic Stem Cells

Abstract 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.