title: BDNF-GSK-3β-β-Catenin Pathway in the mPFC Is Involved in Antidepressant-Like Effects of Morinda officinalis Oligosaccharides in Rats.
abstract: Morinda officinalis oligosaccharides have been reported to exert neuroprotective and antidepressant-like effects in the forced swim test in mice. However, the mechanisms that underlie the antidepressant-like effects of Morinda officinalis oligosaccharides are unclear.
  
  
  
  Chronic unpredictable stress and forced swim test were used to explore the antidepressant-like effects of Morinda officinalis oligosaccharides and resilience to stress in rats. The phosphoinositide-3 kinase inhibitor LY294002 was microinjected in the medial prefrontal cortex to explore the role of glycogen synthase kinase-3β in the antidepressant-like effects of Morinda officinalis oligosaccharides. The expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase 3β, β-catenin, and synaptic proteins was determined in the medial prefrontal cortex and the orbitofrontal cortex by western blot.
  
  
  
  We found that Morinda officinalis oligosaccharides effectively ameliorated chronic unpredictable stress-induced depression-like behaviors in the sucrose preference test and forced swim test. The Morinda officinalis oligosaccharides also significantly rescued chronic unpredictable stress-induced abnormalities in the brain-derived neurotrophic factor-glycogen synthase kinase-3β-β-catenin pathway and synaptic protein deficits in the medial prefrontal cortex but not orbitofrontal cortex. The activation of glycogen synthase kinase-3β by the phosphoinositide-3 kinase inhibitor LY294002 abolished the antidepressant-like effects of Morinda officinalis oligosaccharides in the forced swim test. Naïve rats that were treated with Morinda officinalis oligosaccharides exhibited resilience to chronic unpredictable stress, accompanied by increases in the expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase-3β, and β-catenin in the medial prefrontal cortex.
  
  
  
  Our findings indicate that the brain-derived neurotrophic factor-glycogen synthase kinase-3β-β-catenin pathway in the medial prefrontal cortex may underlie the antidepressant-like effect of Morinda officinalis oligosaccharides and resilience to stress.
authors.affiliation: Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, Beijing, China; National Institute on Drug Dependence, Peking University, Beijing,China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Beijing Zhong Yan Tongrentang Medicine R&D Co., Ltd, Beijing, China; Beijing Tong Ren Tang Co., Ltd, Beijing, China.
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Xu
authors.affiliation: Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, Beijing, China; National Institute on Drug Dependence, Peking University, Beijing,China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Beijing Zhong Yan Tongrentang Medicine R&D Co., Ltd, Beijing, China; Beijing Tong Ren Tang Co., Ltd, Beijing, China.
authors.forename: De-Feng
authors.initials: DF
authors.lastname: Xu
authors.affiliation: Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, Beijing, China; National Institute on Drug Dependence, Peking University, Beijing,China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Beijing Zhong Yan Tongrentang Medicine R&D Co., Ltd, Beijing, China; Beijing Tong Ren Tang Co., Ltd, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.affiliation: Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, Beijing, China; National Institute on Drug Dependence, Peking University, Beijing,China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Beijing Zhong Yan Tongrentang Medicine R&D Co., Ltd, Beijing, China; Beijing Tong Ren Tang Co., Ltd, Beijing, China.
authors.forename: Li-Jing
authors.initials: LJ
authors.lastname: Liu
authors.affiliation: Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, Beijing, China; National Institute on Drug Dependence, Peking University, Beijing,China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Beijing Zhong Yan Tongrentang Medicine R&D Co., Ltd, Beijing, China; Beijing Tong Ren Tang Co., Ltd, Beijing, China.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Sun
authors.affiliation: Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, Beijing, China; National Institute on Drug Dependence, Peking University, Beijing,China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Beijing Zhong Yan Tongrentang Medicine R&D Co., Ltd, Beijing, China; Beijing Tong Ren Tang Co., Ltd, Beijing, China.
authors.forename: Jia-Hui
authors.initials: JH
authors.lastname: Deng
authors.affiliation: Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, Beijing, China; National Institute on Drug Dependence, Peking University, Beijing,China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Beijing Zhong Yan Tongrentang Medicine R&D Co., Ltd, Beijing, China; Beijing Tong Ren Tang Co., Ltd, Beijing, China.
authors.forename: Ruo-Xi
authors.initials: RX
authors.lastname: Zhang
authors.affiliation: Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, Beijing, China; National Institute on Drug Dependence, Peking University, Beijing,China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Beijing Zhong Yan Tongrentang Medicine R&D Co., Ltd, Beijing, China; Beijing Tong Ren Tang Co., Ltd, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yuan
authors.affiliation: Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, Beijing, China; National Institute on Drug Dependence, Peking University, Beijing,China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Beijing Zhong Yan Tongrentang Medicine R&D Co., Ltd, Beijing, China; Beijing Tong Ren Tang Co., Ltd, Beijing, China.
authors.forename: Su-Zhen
authors.initials: SZ
authors.lastname: Zhang
authors.affiliation: Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, Beijing, China; National Institute on Drug Dependence, Peking University, Beijing,China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Beijing Zhong Yan Tongrentang Medicine R&D Co., Ltd, Beijing, China; Beijing Tong Ren Tang Co., Ltd, Beijing, China.
authors.forename: Zhi-Meng
authors.initials: ZM
authors.lastname: Li
authors.affiliation: Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, Beijing, China; National Institute on Drug Dependence, Peking University, Beijing,China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Beijing Zhong Yan Tongrentang Medicine R&D Co., Ltd, Beijing, China; Beijing Tong Ren Tang Co., Ltd, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, Beijing, China; National Institute on Drug Dependence, Peking University, Beijing,China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Beijing Zhong Yan Tongrentang Medicine R&D Co., Ltd, Beijing, China; Beijing Tong Ren Tang Co., Ltd, Beijing, China.
authors.forename: Jin-Sheng
authors.initials: JS
authors.lastname: Li
authors.affiliation: Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, Beijing, China; National Institute on Drug Dependence, Peking University, Beijing,China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Beijing Zhong Yan Tongrentang Medicine R&D Co., Ltd, Beijing, China; Beijing Tong Ren Tang Co., Ltd, Beijing, China.
authors.forename: Su-Hua
authors.initials: SH
authors.lastname: Xie
authors.affiliation: Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, Beijing, China; National Institute on Drug Dependence, Peking University, Beijing,China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Beijing Zhong Yan Tongrentang Medicine R&D Co., Ltd, Beijing, China; Beijing Tong Ren Tang Co., Ltd, Beijing, China.
authors.forename: Su-Xia
authors.initials: SX
authors.lastname: Li
authors.affiliation: Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, Beijing, China; National Institute on Drug Dependence, Peking University, Beijing,China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China; Beijing Zhong Yan Tongrentang Medicine R&D Co., Ltd, Beijing, China; Beijing Tong Ren Tang Co., Ltd, Beijing, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D008297:Male; D032066:Morinda; D009844:Oligosaccharides / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D055500:Resilience, Psychological / Q000187:drug effects; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D009844:Oligosaccharides; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta
keywords: BDNF; GSK-3β; Morinda officinalis oligosaccharides; depression; β-catenin