title: PKA-CREB-BDNF signaling regulated long lasting antidepressant activities of Yueju but not ketamine.
abstract: Yueju confers antidepressant effects in a rapid and long-lasting manner, similar to ketamine. CREB (cAMP-response element binding protein) signaling is implicated in depression pathology and antidepressant responses. However, the role of CREB and associated brain derived neurotrophic factor (BDNF) signaling in rapid and long-lasting antidepressant effects remains unclear. Here, we demonstrated that ICR and Kunming strain mice conferred antidepressant responses lasting for 1 and 5 days, respectively, following a single dose of Yueju. One day post Yueju in Kunming but not ICR strain mice, expression of total and phosphorylated CREB, as well as the CREB signaling activator, PKA (protein kinase A) was up-regulated in the hippocampus. Although BDNF gene expression increased at 3 hours in both strains, it remained up-regulated at 1 day only in Kunming mice. Ketamine showed similar strain-dependent behavioral effects. However, blockade of PKA/CREB signaling blunted the antidepressant effects and reversed the up-regulation of BDNF gene expression by Yueju, but not ketamine. Conversely, blockade of mammalian target of rapamycin signaling led to opposite effects. Taken altogether, prolonged transcriptional up-regulation of hippocampal BDNF may account for the stain-dependent enduring antidepressant responses to Yueju and ketamine, but it was mediated via PKA/CREB pathway only for Yueju.
authors.affiliation: Center for Translational Systems Biology and Neuroscience, Key Laboratory of Integrative Medicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Wenda
authors.initials: W
authors.lastname: Xue
authors.affiliation: School of Psychology, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Center for Translational Systems Biology and Neuroscience, Key Laboratory of Integrative Medicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Gong
authors.affiliation: Center for Translational Systems Biology and Neuroscience, Key Laboratory of Integrative Medicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Hailou
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Center for Translational Systems Biology and Neuroscience, Key Laboratory of Integrative Medicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Tao
authors.affiliation: Center for Translational Systems Biology and Neuroscience, Key Laboratory of Integrative Medicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Xue
authors.affiliation: Center for Translational Systems Biology and Neuroscience, Key Laboratory of Integrative Medicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: School of Psychology, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Fushun
authors.initials: F
authors.lastname: Wang
authors.affiliation: Center for Translational Systems Biology and Neuroscience, Key Laboratory of Integrative Medicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D004365:Drugs, Chinese Herbal; C531537:Yueju-Wan; D007649:Ketamine; D011494:Protein Kinases