Transient receptor potential melastatin 2 governs stress-induced depressive-like behaviors

Seung Yeon Ko, Sung Eun Wang, Han Kyu Lee, Sungsin Jo, Jinil Han, Seung Hoon Lee, Miyeon Choi, Hye Ryeong Jo, Jee Young Seo, Jung Sung Jun, Hyeon Son

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Major 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 Ca 2 + signals; however, the mechanism is poorly understood. Transient receptor potential melastatin type 2 (TRPM2) is a Ca 2+ -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.

Original languageEnglish
Pages (from-to)1770-1775
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number5
DOIs
StatePublished - 2019 Jan 29

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Reactive Oxygen Species
Major Depressive Disorder
Histone Deacetylase 1
Synapsins
Depression
Calpain
Brain
Antidepressive Agents
Cations
Animal Models
Phosphorylation
Phenotype
Gene Expression
Messenger RNA

Keywords

  • Cdk5
  • Depression
  • Neurogenesis
  • ROS
  • TRPM2

Cite this

Ko, Seung Yeon ; Wang, Sung Eun ; Lee, Han Kyu ; Jo, Sungsin ; Han, Jinil ; Lee, Seung Hoon ; Choi, Miyeon ; Jo, Hye Ryeong ; Seo, Jee Young ; Jun, Jung Sung ; Son, Hyeon. / Transient receptor potential melastatin 2 governs stress-induced depressive-like behaviors. In: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; Vol. 116, No. 5. pp. 1770-1775.
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Transient receptor potential melastatin 2 governs stress-induced depressive-like behaviors. / Ko, Seung Yeon; Wang, Sung Eun; Lee, Han Kyu; Jo, Sungsin; Han, Jinil; Lee, Seung Hoon; Choi, Miyeon; Jo, Hye Ryeong; Seo, Jee Young; Jun, Jung Sung; Son, Hyeon.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 5, 29.01.2019, p. 1770-1775.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Jo, Sungsin

AU - Han, Jinil

AU - Lee, Seung Hoon

AU - Choi, Miyeon

AU - Jo, Hye Ryeong

AU - Seo, Jee Young

AU - Jun, Jung Sung

AU - Son, Hyeon

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