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TRPV4 inhibitor HC067047 produces antidepressant-like effect in LPS-induced depression mouse model

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机构： [1]Clinical Anatomy & Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, 421001, Hengyang, Hunan, China [2]Institute of Neuroscience, Hengyang Medical School, University of South China, 421001, Hengyang, Hunan, China [3]Department of Pathology, Hengyang Medical School, University of South China, 421001, Hengyang, Hunan, China [4]Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, 421001, Hengyang, Hunan, China [5]Department of Anatomy & Histology & Embryology, Kunming Medical University, 650500, Kunming, Yunnan, China [6]Key Laboratory of Brain Science Research & Transformation in Tropical Environment of Hainan Province, Hainan Medical University, 571199, Haikou, China

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Inflammation is a crucial component that contributes to the pathogenesis of major depressive disorder. It has been revealed that the nonselective cation channel transient receptor potential vanilloid 4 (TRPV4) profoundly affects a variety of physiological processes, including inflammation. However, its roles and mechanisms in LPS-induced depression are still unclear. Here, for the first time, we found that there was a significant increase in TRPV4 in the hippocampus in a depression mouse model induced by LPS. TRPV4 inhibitor HC067047 or knockdown the hippocampal TRPV4 with TRPV4 shRNA could effectively rescue the aberrant behaviors. Furthermore, TRPV4 inhibitor HC067047 reduced the activation of astrocyte and microglia, decreased expression of CaMKII-NLRP3 inflammasome and increased the expression of neurogenesis marker DCX in the hippocampus. In addition, enhanced neuroinflammation in the serum was also reversed by TRPV4 inhibitor HC067047. Thus, we consider that TRPV4 has an important role in contributing to the depression-like behavior following LPS-induced systemic inflammation.Copyright © 2021. Published by Elsevier Ltd.

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出版当年[2021]版：

大类 | 2 区医学

小类 | 2 区神经科学 2 区药学

最新[2025]版：

大类 | 2 区医学

小类 | 2 区药学 3 区神经科学

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第一作者机构： [1]Clinical Anatomy & Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, 421001, Hengyang, Hunan, China

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通讯机构： [1]Clinical Anatomy & Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, 421001, Hengyang, Hunan, China [6]Key Laboratory of Brain Science Research & Transformation in Tropical Environment of Hainan Province, Hainan Medical University, 571199, Haikou, China [*1]Key Laboratory of Brain Science Research & Transformation in Tropical Environment of Hainan Province, Hainan Medical University, 571199, Haikou, China.

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