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

Title
Transient receptor potential melastatin 2 governs stress-induced depressive-like behaviors
Author
정승준
Keywords
TRPM2; depression; ROS; Cdk5; neurogenesis
Issue Date
2019-01
Publisher
NATL ACAD SCIENCES
Citation
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 116, NO. 5, Page. 1770-1775
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 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.
URI
https://www.pnas.org/content/116/5/1770https://repository.hanyang.ac.kr/handle/20.500.11754/106125
ISSN
0027-8424
DOI
10.1073/pnas.1814335116
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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