title: Tetramethylpyrazine Produces Antidepressant-Like Effects in Mice Through Promotion of BDNF Signaling Pathway.
abstract: BACKGROUND
  Current antidepressants are clinically effective only after several weeks of administration. Tetramethylpyrazine (TMP) is an identified component of Ligusticum wallichii with neuroprotective effects. Here, we investigated the antidepressant effects of TMP in mice models of depression.
  
  
  METHODS
  Antidepressant effects of TMP were first detected in the forced swim test (FST) and tail suspension test (TST), and further assessed in the chronic social defeat stress (CSDS) model. Changes in the brain-derived neurotrophic factor (BDNF) signaling pathway and in hippocampal neurogenesis after CSDS and TMP treatment were then investigated. A tryptophan hydroxylase inhibitor and BDNF signaling inhibitors were also used to determine the mechanisms of TMP.
  
  
  RESULTS
  TMP exhibited potent antidepressant effects in the FST and TST without affecting locomotor activity. TMP also prevented the CSDS-induced symptoms. Moreover, TMP completely restored the CSDS-induced decrease of BDNF signaling pathway and hippocampal neurogenesis. Furthermore, a blockade of the BDNF signaling pathway prevented the antidepressant effects of TMP, while TMP produced no influence on the monoaminergic system.
  
  
  CONCLUSIONS
  In conclusion, these data provide the first evidence that TMP has antidepressant effects, and this was mediated by promoting the BDNF signaling pathway.
authors.affiliation: Department of Pharmacology, Pharmacy College, Nantong University, Nantong 226001, Jiangsu, China (Drs Jiang, Huang, Chen, Tong, and Zhang).
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, Pharmacy College, Nantong University, Nantong 226001, Jiangsu, China (Drs Jiang, Huang, Chen, Tong, and Zhang).
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Pharmacy College, Nantong University, Nantong 226001, Jiangsu, China (Drs Jiang, Huang, Chen, Tong, and Zhang).
authors.forename: Xiang-Fan
authors.initials: XF
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Pharmacy College, Nantong University, Nantong 226001, Jiangsu, China (Drs Jiang, Huang, Chen, Tong, and Zhang).
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Tong
authors.affiliation: Department of Pharmacology, Pharmacy College, Nantong University, Nantong 226001, Jiangsu, China (Drs Jiang, Huang, Chen, Tong, and Zhang) huanghezhi36020@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D011719:Pyrazines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D011719:Pyrazines; D014365:Tryptophan Hydroxylase; C017953:tetramethylpyrazine
keywords: brain-derived neurotrophic factor; chronic social defeat stress; depression; hippocampal neurogenesis; tetramethylpyrazine