title: Rosmarinic acid ameliorates depressive-like behaviors in a rat model of CUS and Up-regulates BDNF levels in the hippocampus and hippocampal-derived astrocytes.
abstract: 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 μg/mL) or U0126 (2 μM as a final concentration) + RA (sham, 1, 5, 10, 20, and 40 μg/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 μg/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.
authors.affiliation: Department of Psychology, School of Aerospace Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Jin
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Fengchi
authors.initials: F
authors.lastname: Yang
authors.forename: Ya-Hong
authors.initials: YH
authors.lastname: Zhang
authors.forename: Danmin
authors.initials: D
authors.lastname: Miao
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002934:Cinnamates / Q000494:pharmacology*; D053630:Depsides / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological; D015854:Up-Regulation / Q000187:drug effects*; D000097123:Rosmarinic Acid
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002934:Cinnamates; D053630:Depsides; D000097123:Rosmarinic Acid