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Stress‐induced depression‐ and anxiety‐like behaviors are associated with the imbalance of redox state: the protective effect of PDE2 inhibition (1144.3)
Author(s) -
Xu Ying,
Ruan Lina,
Zhang Hanting,
O'Donnell James
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1144.3
Subject(s) - oxidative stress , reactive oxygen species , superoxide dismutase , chemistry , protein kinase a , pharmacology , kinase , biology , biochemistry
The correspondence between the prevalence of exposure to oxidative stress and the development of depression/anxiety is lacking. Chronic stress alters the expression of genes affecting redox state, such as excess levels of reactive oxygen species (ROS) and reduced superoxide dismutase (SOD) expression, which induce functional abnormalities in the brain. Phosphodiesterase 2 (PDE2) is highly expressed in the limbic system, which may play an important role in both the development and the treatment of stress‐related depression. The present study investigated the relationship between PDE2 activity and the ROS expression after stress and how PDE2 inhibitor and PDE2 silence regulate stress‐induced depression/anxiety‐like behaviors through affecting redox state. The results suggested that corticosterone‐induced ROS expression was positively related to PDE2 levels, which was consistent with in vivo data. Pretreatment with protein kinase G inhibitor KT5823, but not protein kinase A inhibitor H89, reversed the effect of PDE2 inhibition, suggesting the involvement of cGMP‐dependent signaling. This study provides the evidence that PDE2 inhibition may represent a novel therapeutic target for stress‐related psychiatric disorders.