Cyclooxygenase-2 Signalling Pathway in the Cortex is Involved in the Pathophysiological Mechanisms in the Rat Model of Depression
Open accessAbstract
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.
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Both MDD patients and animal models of depression show a remarkable reduction in serum BDNF levels.
“Both MDD patients [57–59] and animal models of depression [60, 61] show a remarkable reduction in serum BDNF levels.”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [60]
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- Authors
- Chen, Q., Luo, Y., Kuang, S., Yang, Y., Tian, X., Ma, J., Mai, S., Xue, L., & Yang, J.
- Affiliations
- Chongqing Medical University (CN)
- Corresponding author
- Yang, Junqing
- Venue
- Scientific Reports
- Published
- 2017-03-28
- Volume
- 7
- Issue
- 1
- Pages
- 488-488
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5428817
- OpenAlex
- W2601735476
- Cited by
- 49
- References
- 39
- Citations by year
- 2025: 6 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 8 · 2020: 5 · 2019: 11 · 2018: 5
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- cyclooxygenase-2, depression, chronic unpredictable mild stress, prostaglandin E2, brain-derived neurotrophic factor, meloxicam, oxidative stress, inflammatory cytokines, depression-like behavior, rat model of depression
- MeSH terms
- Meloxicam, Cyclic AMP, Animals, Behavior, Animal, Cerebral Cortex, Depression, Disease Models, Animal, Gene Expression Regulation, Male, Superoxide Dismutase, Thiazines, Thiazoles, Dinoprostone, Signal Transduction, Cytokines, Cyclooxygenase Inhibitors, Cyclic AMP Response Element-Binding Protein, Cyclic AMP-Dependent Protein Kinases, Brain-Derived Neurotrophic Factor, RNA Interference, Rats, Cyclooxygenase 2
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