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Proc. Natl. Acad. Sci. USA, Published ahead of print January 14, 2019 | https://doi.org/10.1073/pnas.1814335116 Transient receptor potential melastatin 2 governs stress-induced depressive-like behaviors

Seung Yeon Ko^a,b, Sung Eun Wang^a,b, Han Kyu Lee^a,b, Sungsin Jo^c, Jinil Han^d, Seung Hoon Lee^a,b, Miyeon Choi^a,b, Hye-Ryeong Jo^a,b, Jee Young Seo^a,b, Sung Jun Jung^a,b,e,1, and Hyeon Son^a,b,f,1

^a Graduate School of Biomedical Science and Engineering, Hanyang University, Seongdong-gu, Seoul 04763, Korea; ^b Hanyang Biomedical Research Institute, Hanyang University, Seongdong-gu, Seoul 04763, Korea; ^c Hanyang University Hospital for Rheumatic Diseases, Seongdong-gu, Seoul 04763, Korea; ^d Gencurix, Inc., Guro-gu, Seoul 08394, Korea; ^e Department of Physiology, College of Medicine, Hanyang University, Seongdong-gu, Seoul 04763, Korea; and ^f Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seongdong-gu, Seoul 04763, Korea

¹To whom correspondence may be addressed.

Abstract

ajor depressive disorder (MDD) is a devastating disease that arises in a background of environmental risk factors, such as chronic stress, that produce reactive oxygen species (ROS) in the brain. The chronic stress-induced ROS production involves Ca²⁺ signals; however, the mechanism is poorly understood. Transient receptor potential melastatin type 2 (TRPM2) is a Ca²⁺-permeable cation channel that is highly expressed in the brain. Here we show that in animal models of chronic unpredictable stress (CUS), deletion of TRPM2 (Trpm2^-/-) produces antidepressant-like behaviors in mice. This phenotype correlates with reduced ROS, ROS-induced calpain activation, and enhanced phosphorylation of two Cdk5 targets including synapsin 1 and histone deacetylase 5 that are linked to synaptic function and gene expression, respectively. Moreover, TRPM2 mRNA expression is increased in hippocampal tissue samples from patients with MDD. Our findings suggest that TRPM2 is a key agent in stress-induced depression and a possible target for treating depression.

TRPM2 | depression | ROS | Cdk5 | neurogenesis

논문정보

형식Research article
게재일2019년 01월 (BRIC 등록일 2019-01-21)
연구진국내 연구진
분야 의약학 > 신경의학

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