title: The antidepressant-like effects of biperiden may involve BDNF/TrkB signaling-mediated BICC1 expression in the hippocampus and prefrontal cortex of mice.
abstract: Preclinical and clinical studies suggest that neuronal muscarinic acetylcholine receptor (M-AchR) antagonists have antidepressant-like properties. Despite the recent interest in bicaudal C homolog 1 gene (BICC1) as a target for the treatment of depression, the upstream signaling molecules that regulate BICC1 are unknown, and very few studies have addressed the involvement of BICC1 in the antidepressant-like effects of the selective M1-AchR inhibitor, biperiden. Growing evidence indicates that activation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase receptor B (TrkB) signaling may be involved in antidepressant-like activities. In this study, we investigated the role of BDNF/TrkB signaling in the regulation of BICC1 expression in the chronic unpredictable stress (CUS) mouse model of depression. Furthermore, we also examined whether BDNF/TrkB signaling contributes to the antidepressant-like effects of biperiden via down-regulation of BICC1 in the hippocampus and prefrontal cortex of mice. Our current data show that CUS exposure induced significant depression-like behaviors, down-regulation of BDNF/TrkB signaling and up-regulation of BICC1 in the hippocampus and prefrontal cortex of mice. However, biperiden significantly alleviated the CUS-induced abnormalities. Moreover, we found that the effects of biperiden were antagonized by pretreatment with the TrkB antagonist K252a. Our results indicate that BDNF/TrkB signaling may be the major upstream mediator of BICC1 involvement in the antidepressant-like effects of biperiden.
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang 315201, PR China; Ningbo Key Laboratory of Behavioral Neuroscience, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Hongqi Hospital, Mudanjiang Medical College, Mudanjiang, Heilongjiang 157011, PR China.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang 315201, PR China; Ningbo Key Laboratory of Behavioral Neuroscience, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: Lingjiang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang 315201, PR China; Ningbo Key Laboratory of Behavioral Neuroscience, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: Chenli
authors.initials: C
authors.lastname: Li
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang 315201, PR China; Ningbo Key Laboratory of Behavioral Neuroscience, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Li
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang 315201, PR China; Ningbo Key Laboratory of Behavioral Neuroscience, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: Hanjie
authors.initials: H
authors.lastname: Yu
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang 315201, PR China; Ningbo Key Laboratory of Behavioral Neuroscience, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: Xiongxiong
authors.initials: X
authors.lastname: Cai
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang 315201, PR China; Ningbo Key Laboratory of Behavioral Neuroscience, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang 315201, PR China; Ningbo Key Laboratory of Behavioral Neuroscience, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: Xinbei
authors.initials: X
authors.lastname: Shen
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang 315201, PR China; Ningbo Key Laboratory of Behavioral Neuroscience, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: Jinting
authors.initials: J
authors.lastname: Wang
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang 315201, PR China; Ningbo Key Laboratory of Behavioral Neuroscience, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China.
authors.forename: Jiacheng
authors.initials: J
authors.lastname: Geng
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang 315201, PR China; Ningbo Key Laboratory of Behavioral Neuroscience, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China. Electronic address: wangchuang@nbu.edu.cn.
authors.forename: Chuang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Ningbo Kangning Hospital, Ningbo, Zhejiang 315201, PR China; Ningbo Key Laboratory of Behavioral Neuroscience, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang 315211, PR China. Electronic address: shi-yaosheng@163.com.
authors.forename: Yaosheng
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001712:Biperiden / Q000494:pharmacology / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D026121:Indole Alkaloids / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; C540667:Bicc1 protein, mouse; D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D026121:Indole Alkaloids; D016601:RNA-Binding Proteins; D001712:Biperiden; C049985:staurosporine aglycone; D020813:Receptor, trkB
keywords: BDNF/TrkB signaling; Bicaudal C homolog 1 gene (BICC1); Biperiden; Depression