title: Chronic unpredictable mild stress induces parallel reductions of 15-PGDH in the hypothalamus and lungs in rats.
abstract: Prostaglandin E2 (PGE2) is an important inflammatory mediator and considered to be involved in the pathophysiology of depression. Previous studies that investigated the role of PGE2 in depression solely concentrated on the cyclooxygenase-dependent synthesis of this bioactive lipid. However, enzymes that degrade PGE2, such as NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH), have not yet been explored. The present study examined the expression of 15-PGDH in an animal model of depression. Depressive-like behaviors were measured after rats were exposed to chronic unpredictable mild stress (CUMS). 15 PGDH mRNA and protein expression and activity and PGE2 levels were detected in the brain and lungs in stressed animals. The stressed animals exhibited decreases in body weight gain, locomotor activity in the open field, and sucrose preference. The hypothalamus and lungs had high baseline 15-PGDH mRNA and protein expression, whereas the frontal cortex and hippocampus showed no detectable 15-PGDH mRNA or protein expression. 15 PGDH mRNA and protein expression was significantly downregulated in the hypothalamus and lungs in stressed rats compared with control rats, and the enzymatic activity of 15-PGDH was correlated with protein expression levels. PGE2 concentrations in the brain and serum increased in stressed rats. These results suggest the loss of 15-PGDH expression in depression, and 15-PGDH may be a novel potential pharmacological target for the treatment of depression.
authors.affiliation: Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jian-You
authors.initials: JY
authors.lastname: Guo
authors.affiliation: The Medical Experimental Center of Nanyang Institute of Technology, Nanyang 473004, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Bian
authors.affiliation: Department of Pharmacy, Zhejiang Medical College, Hangzhou 310053, China. Electronic address: 6991765@qq.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yao
mesh_terms: D000818:Animals; D001835:Body Weight; D002908:Chronic Disease; D003866:Depressive Disorder / Q000201:enzymology*; D019422:Dietary Sucrose / Q000008:administration & dosage; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D005106:Exploratory Behavior; D005625:Frontal Lobe / Q000201:enzymology; D006624:Hippocampus / Q000201:enzymology; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism*; D007031:Hypothalamus / Q000201:enzymology*; D008168:Lung / Q000201:enzymology*; D008297:Male; D009043:Motor Activity; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000201:enzymology*; D055697:Taste Perception; D035501:Uncertainty
chemical_list: D019422:Dietary Sucrose; D012333:RNA, Messenger; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D015232:Dinoprostone
keywords: 15-PGDH; Anhedonia; Hypothalamus; Prostaglandin E(2); Stress