title: Cyclooxygenase-2 Signalling Pathway in the Cortex is Involved in the Pathophysiological Mechanisms in the Rat Model of Depression.
abstract: This study was designed to investigate the effect of the cortical cyclooxygenase-2 (COX2) pathway on depressive behaviour in rats. Meloxicam, COX2 overexpressed lentivirus and COX2 RNAi lentivirus were administered to Sprague-Dawley rats subjected to chronic unpredictable mild stress (CUMS). Behaviour tests, biochemistry and immunohistochemistry methods, enzyme-linked immunosorbent assays, western blotting and reverse transcription polymerase chain reactions were used to evaluate the changes in rat behaviour and the cortical COX2 pathway. CUMS rats showed depressive-like behaviours. The superoxide dismutase activity and cyclic adenosine monophosphate (cAMP) contents were significantly decreased, the contents of malondialdehyde, prostaglandin E2 (PGE2) and inflammatory cytokines were significantly increased. The expressions of protein kinase A (PKA) and cAMP response element-binding protein (CREB) were decreased, and the levels of brain-derived neurotrophic factor (BDNF) and COX2 were significantly increased. Meloxicam and COX2 RNAi lentivirus significantly alleviated the abnormalities induced by CUMS, while COX2 overexpressed lentivirus aggravated these abnormalities. Our results indicated that the cortical COX2 pathway was activated in CUMS rats. Inhibition of COX2 activity/expression can obviously improve depressive behaviours in CUMS rats. Upregulating COX2 expression can increase the susceptibility of rats to CUMS. An imbalance in the cortical COX2-PGE2-cAMP/PKA-CREB-BDNF signalling pathway participates in the pathogenic mechanism of depression.
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Kuang
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
authors.forename: Shaoshan
authors.initials: S
authors.lastname: Mai
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China. 1139627371@qq.com.
authors.forename: Junqing
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology*; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003863:Depression / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D008297:Male; D000077239:Meloxicam; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D013843:Thiazines; D013844:Thiazoles; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone; D000077239:Meloxicam