PMID- 23756732 OWN - NLM STAT- MEDLINE DCOM- 20140310 LR - 20231213 IS - 1573-6903 (Electronic) IS - 0364-3190 (Linking) VI - 38 IP - 9 DP - 2013 Sep TI - Rosmarinic acid ameliorates depressive-like behaviors in a rat model of CUS and Up-regulates BDNF levels in the hippocampus and hippocampal-derived astrocytes. PG - 1828-37 LID - 10.1007/s11064-013-1088-y [doi] AB - Rosmarinic acid (RA), a primary constituent of a Chinese herbal medicine, has been shown to have some therapeutic effects in an animal model of depression, but its underlying mechanisms are poorly understood. Sprague-Dawley rats were exposed to chronic unpredictable stress (CUS) for 21 days, and received RA for 14 days from the last week of CUS, then the behavioral changes, hippocampal pERK1/2 and BDNF levels were observed. Rats were further treated with U0126 (an ERK1/2 phosphorylation inhibitor) 30 min before RA treatment to assess the effects of RA and ERK1/2 signaling in depressive-like behavior and hippocampal BDNF levels. In addition, brains of newly born Sprague-Dawley rats were used to harvest and expand hippocampal astrocytes. Cells were exposed to different concentrations of RA (sham, 1, 5, 10, 20, and 40 mug/mL) or U0126 (2 muM as a final concentration) + RA (sham, 1, 5, 10, 20, and 40 mug/mL) for 48 h, and the pERK1/2 and BDNF levels were assessed by western and ELISA assays. RA administration (10 mg/kg daily) reversed depressive-like behaviors in rats exposed to a chronic unpredictable stress paradigm and restored pERK1/2 protein expression and hippocampal brain-derived neurotrophic factor (BDNF). Moreover, in vitro experiments revealed that 20 mug/mL RA increased pERK1/2 and BDNF levels in cultured astrocytes. Interestingly, the effects of RA were inhibited by U0126. RA might be a useful treatment for depression and the changes in ERK1/2 signaling and BDNF levels may play a critical role in the pharmacological action of RA. FAU - Jin, Xiang AU - Jin X AD - Department of Psychology, School of Aerospace Medicine, Fourth Military Medical University, Xi'an, 710032, China. FAU - Liu, Peng AU - Liu P FAU - Yang, Fengchi AU - Yang F FAU - Zhang, Ya-Hong AU - Zhang YH FAU - Miao, Danmin AU - Miao D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130612 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cinnamates) RN - 0 (Depsides) SB - IM MH - Animals MH - Astrocytes/*drug effects/metabolism MH - Behavior, Animal/drug effects MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cinnamates/*pharmacology MH - Depsides/*pharmacology MH - Enzyme-Linked Immunosorbent Assay MH - Hippocampus/*drug effects/metabolism/pathology MH - Male MH - Rats MH - Rats, Sprague-Dawley MH - *Stress, Psychological MH - Up-Regulation/*drug effects MH - Rosmarinic Acid EDAT- 2013/06/13 06:00 MHDA- 2014/03/13 06:00 CRDT- 2013/06/13 06:00 PHST- 2013/03/30 00:00 [received] PHST- 2013/05/25 00:00 [accepted] PHST- 2013/05/22 00:00 [revised] PHST- 2013/06/13 06:00 [entrez] PHST- 2013/06/13 06:00 [pubmed] PHST- 2014/03/13 06:00 [medline] AID - 10.1007/s11064-013-1088-y [doi] PST - ppublish SO - Neurochem Res. 2013 Sep;38(9):1828-37. doi: 10.1007/s11064-013-1088-y. Epub 2013 Jun 12.