The antidepressant-like effects of biperiden may involve BDNF/TrkB signaling-mediated BICC1 expression in the hippocampus and prefrontal cortex of mice

作者：Zhou, Dongsheng; Zhang, Zhongmin; Liu, Lingjiang; Li, Chenli; Li, Mengmeng; Yu, Hanjie; Cai, Xiongxiong; Sun, Xin; Shen, Xinbei; Wang, Jinting; Geng, Jiacheng; Wang, Chuang^*; Shi, Yaosheng^*

来源：Pharmacology Biochemistry and Behavior, 2017, 157: 47-57.

DOI：10.1016/j.pbb.2017.02.004

• Biperiden
• Depression
• BDNF/TrkB signaling
• Bicaudal C homolog 1 gene (BICC1)

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.

• 出版日期2017-6
• 单位宁波大学; 牡丹江医学院