• Dongsheng Zhou, Zhongmin Zhang, Lingjiang Liu, Chenli Li, Mengmeng Li, Hanjie Yu, Xiongxiong Cai, Xin Sun, Xinbei Shen, Jinting Wang, Jiacheng Geng, Chuang Wang, and Yaosheng Shi.
• 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.
• Pharmacol. Biochem. Behav. 2017 Jun 1; 157: 47-57.

AbstractPreclinical 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.Copyright © 2017 Elsevier Inc. All rights reserved.

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