Shen Peng, Hu Qingchuan, Dong Meixue, Bai Shunjie, Liang Zihong, Chen Zhi, Li Pengfei, Hu Zicheng, Zhong Xiaogang, Zhu Dan, Wang Haiyang, Xie Peng
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
Chongqing Key Laboratory of Neurobiology, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
Behav Brain Res. 2017 Sep 29;335:63-70. doi: 10.1016/j.bbr.2017.08.011. Epub 2017 Aug 8.
Serotonin noradrenaline reuptake inhibitors are effective antidepressant drugs, which include venlafaxine and duloxetine. Venlafaxine is commonly used in a clinical context, but the molecular biological mechanisms behind its effects have not been fully determined. Here, we explored the potential biological effects of venlafaxine on mouse hippocampus. Mice were randomly divided into two groups and injected daily with 0.9% NaCl solution or venlafaxine. A GC-MS-based metabolomic approach was used to identify possible metabolic differences between these groups, and the key proteins involved in the relevant pathways were validated by western blotting. In our experiments, 27 hippocampal metabolites that distinguished the venlafaxine group from the control group were identified. These differential metabolites were subjected to Ingenuity Pathway Analysis, which revealed that they were strongly related to two metabolic pathways (MAPK-ERK1/2 and P13K-AKT signaling pathways). Six key proteins, BDNF, p-c-Raf, p-MAPK, p-MEK, p-AKT, and CREB, were verified by western blotting and the results were consistent with the differential metabolites identified by GC-MS. This study sheds light on the biological mechanisms underlying the effects of venlafaxine.
5-羟色胺去甲肾上腺素再摄取抑制剂是有效的抗抑郁药物，包括文拉法辛和度洛西汀。文拉法辛在临床中常用，但其作用背后的分子生物学机制尚未完全明确。在此，我们探究了文拉法辛对小鼠海马体的潜在生物学效应。将小鼠随机分为两组，每天分别注射0.9%氯化钠溶液或文拉法辛。采用基于气相色谱-质谱联用的代谢组学方法来识别两组之间可能存在的代谢差异，并通过蛋白质印迹法验证相关途径中涉及的关键蛋白。在我们的实验中，鉴定出了27种可区分文拉法辛组和对照组的海马体代谢物。对这些差异代谢物进行了 Ingenuity 通路分析，结果显示它们与两条代谢途径（MAPK-ERK1/2和P13K-AKT信号通路）密切相关。通过蛋白质印迹法验证了6种关键蛋白，即脑源性神经营养因子（BDNF）、磷酸化c-Raf、磷酸化丝裂原活化蛋白激酶（p-MAPK）、磷酸化丝裂原活化蛋白激酶激酶（p-MEK）、磷酸化蛋白激酶B（p-AKT）和环磷腺苷效应元件结合蛋白（CREB），结果与气相色谱-质谱联用鉴定出的差异代谢物一致。本研究揭示了文拉法辛作用的生物学机制。
