CNS neuroscience & therapeutics, 2018-10, Vol.24 (10), p.917-929
2018
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- Autor(en) / Beteiligte
- Titel
- PGE2‐EP3 signaling exacerbates hippocampus‐dependent cognitive impairment after laparotomy by reducing expression levels of hippocampal synaptic plasticity‐related proteins in aged mice
- Ist Teil von
- CNS neuroscience & therapeutics, 2018-10, Vol.24 (10), p.917-929
- Ort / Verlag
- England: John Wiley & Sons, Inc
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Summary Aim Multifactors contribute to the development of postoperative cognitive dysfunction (POCD), of which the most important mechanism is neuroinflammation. Prostaglandin E2 (PGE2) is a key neuroinflammatory molecule and could modulate hippocampal synaptic transmission and plasticity. This study was designed to investigate whether PGE2 and its receptors signaling pathway were involved in the pathophysiology of POCD. Methods Sixteen‐month old male C57BL/6J mice were exposed to laparotomy. Cognitive function was evaluated by fear conditioning test. The levels of PGE2 and its 4 distinct receptors (EP1‐4) were assessed by biochemical analysis. Pharmacological or genetic methods were further applied to investigate the role of the specific PGE2 receptors. Results Here, we found that the transcription and translation level of the EP3 receptor in hippocampus increased remarkably, but not EP1, EP2, or EP4. Immunofluorescence results showed EP3 positive cells in the hippocampal CA1 region were mainly neurons. Furthermore, pharmacological blocking or genetic suppression of EP3 could alleviate surgery‐induced hippocampus‐dependent memory deficits and rescued the expression of plasticity‐related proteins, including cAMP response element‐binding protein (CREB), activity‐regulated cytoskeletal‐associated protein (Arc), and brain‐derived neurotrophic factor (BDNF) in hippocampus. Conclusion This study showed that PGE2‐EP3 signaling pathway was involved in the progression of POCD and identified EP3 receptor as a promising treatment target.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1755-5930eISSN: 1755-5949DOI: 10.1111/cns.12832Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6490074
- Format
- –
- Schlagworte
- Aging, AIDS-Related Complex - genetics, AIDS-Related Complex - metabolism, Animals, Biochemical analysis, Brain-derived neurotrophic factor, Brain-Derived Neurotrophic Factor - genetics, Brain-Derived Neurotrophic Factor - metabolism, Cognition Disorders - etiology, Cognition Disorders - pathology, Cognitive ability, Conditioning, Psychological, CREB-Binding Protein - genetics, CREB-Binding Protein - metabolism, Cyclic AMP response element-binding protein, Cytoskeleton, Dinoprostone - metabolism, Exploratory Behavior, Fear, Fear conditioning, Gene Expression Regulation - physiology, Genetic analysis, Genetic suppression, Hippocampal plasticity, Hippocampus, Hippocampus - metabolism, Immunofluorescence, Inflammation, Laparotomy - adverse effects, Male, Memory, Mice, Mice, Inbred C57BL, neuroinflammation, Original, postoperative cognitive dysfunction, Postoperative Complications - pathology, Postoperative Complications - physiopathology, Prostaglandin E2, Receptors, Prostaglandin E, EP3 Subtype - metabolism, RNA, Messenger - metabolism, Signal Detection, Psychological - physiology, Signal transduction, Surgery, Synaptic plasticity, synaptic plasticity‐related protein, Synaptic transmission, Transcription, Transduction, Genetic