PMID- 28352129
OWN - NLM
STAT- MEDLINE
DCOM- 20180830
LR  - 20181202
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Mar 28
TI  - Cyclooxygenase-2 Signalling Pathway in the Cortex is Involved in the 
      Pathophysiological Mechanisms in the Rat Model of Depression.
PG  - 488
LID - 10.1038/s41598-017-00609-7 [doi]
LID - 488
AB  - 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.
FAU - Chen, Qi
AU  - Chen Q
AD  - Department of Pharmacology, Chongqing Medical University, the Key Laboratory of 
      Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
FAU - Luo, Ying
AU  - Luo Y
AD  - Department of Pharmacology, Chongqing Medical University, the Key Laboratory of 
      Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
FAU - Kuang, Shengnan
AU  - Kuang S
AD  - Department of Pharmacology, Chongqing Medical University, the Key Laboratory of 
      Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
FAU - Yang, Yang
AU  - Yang Y
AD  - Department of Pharmacology, Chongqing Medical University, the Key Laboratory of 
      Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
FAU - Tian, Xiaoyan
AU  - Tian X
AD  - Department of Pharmacology, Chongqing Medical University, the Key Laboratory of 
      Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
FAU - Ma, Jie
AU  - Ma J
AD  - Department of Pharmacology, Chongqing Medical University, the Key Laboratory of 
      Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
FAU - Mai, Shaoshan
AU  - Mai S
AD  - Department of Pharmacology, Chongqing Medical University, the Key Laboratory of 
      Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
FAU - Xue, Lai
AU  - Xue L
AD  - Department of Pharmacology, Chongqing Medical University, the Key Laboratory of 
      Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
FAU - Yang, Junqing
AU  - Yang J
AD  - Department of Pharmacology, Chongqing Medical University, the Key Laboratory of 
      Biochemistry and Molecular Pharmacology, Chongqing, 400016, China. 
      1139627371@qq.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170328
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Cytokines)
RN  - 0 (Thiazines)
RN  - 0 (Thiazoles)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - VG2QF83CGL (Meloxicam)
SB  - IM
MH  - Animals
MH  - Behavior, Animal
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cerebral Cortex/*metabolism/*physiopathology
MH  - Cyclic AMP/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Cyclooxygenase 2/genetics/*metabolism
MH  - Cyclooxygenase Inhibitors/pharmacology
MH  - Cytokines/metabolism
MH  - Depression/genetics/*metabolism/physiopathology/*psychology
MH  - Dinoprostone/metabolism
MH  - Disease Models, Animal
MH  - Gene Expression Regulation
MH  - Male
MH  - Meloxicam
MH  - RNA Interference
MH  - Rats
MH  - *Signal Transduction
MH  - Superoxide Dismutase/metabolism
MH  - Thiazines/pharmacology
MH  - Thiazoles/pharmacology
PMC - PMC5428817
COIS- The authors declare that they have no competing interests.
EDAT- 2017/03/30 06:00
MHDA- 2018/08/31 06:00
PMCR- 2017/03/28
CRDT- 2017/03/30 06:00
PHST- 2016/10/28 00:00 [received]
PHST- 2017/03/07 00:00 [accepted]
PHST- 2017/03/30 06:00 [entrez]
PHST- 2017/03/30 06:00 [pubmed]
PHST- 2018/08/31 06:00 [medline]
PHST- 2017/03/28 00:00 [pmc-release]
AID - 10.1038/s41598-017-00609-7 [pii]
AID - 609 [pii]
AID - 10.1038/s41598-017-00609-7 [doi]
PST - epublish
SO  - Sci Rep. 2017 Mar 28;7(1):488. doi: 10.1038/s41598-017-00609-7.