PGE2-EP3 signaling exacerbates hippocampus-dependent cognitive impairment after laparotomy by reducing expression levels of hippocampal synaptic plasticity-related proteins in aged mice

Autor: Jing-Yu Xiao, Xuebi Tian, Hong-Bing Xiang, Yu-Ke Tian, Wenchang Zhou, Anne Manyande, Bingrui Xiong, Wen Zhang, Hui Yang, Feng Gao
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Aging
Signal Detection
Psychological
Prostaglandin E2 receptor
Hippocampal formation
Neurotransmission
psychology
CREB
Hippocampus
Dinoprostone
Mice
03 medical and health sciences
Postoperative Complications
0302 clinical medicine
AIDS-Related Complex
Transduction
Genetic
Physiology (medical)
Conditioning
Psychological
medicine
Animals
Pharmacology (medical)
RNA
Messenger
Receptor
Pharmacology
Brain-derived neurotrophic factor
Laparotomy
biology
Brain-Derived Neurotrophic Factor
health
Fear
Original Articles
medicine.disease
CREB-Binding Protein
Mice
Inbred C57BL
Psychiatry and Mental health
030104 developmental biology
Gene Expression Regulation
Receptors
Prostaglandin E
EP3 Subtype
Exploratory Behavior
biology.protein
lipids (amino acids
peptides
and proteins)
Signal transduction
Cognition Disorders
Neuroscience
Postoperative cognitive dysfunction
030217 neurology & neurosurgery
ISSN: 1755-5930
Popis: Aim: Multi factors 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\ud receptors signaling pathway were involved in the pathophysiology of POCD.\ud \ud 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 four 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.\ud \ud Results: Here, we found that the transcription and translation level of 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 hippocampu dependent memory deficit , 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.
Databáze: OpenAIRE
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