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

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Xiao, J, Xiong, B, Zhang, W, Zhou, W, Yang, H, Gao, F, Xiang, H, Manyande, Anne ORCID: https://orcid.org/0000-0002-8257-0722, Tian, X and Tian, Y (2018) PGE2-EP3 signaling exacerbates hippocampus-dependent cognitive impairment after laparotomy by reducing expression levels of hippocampal synaptic plasticity-related proteins in aged mice. CNS Neuroscience & Therapeutics, 24 (10). pp. 917-929. ISSN 1755-5930

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Official URL: https://doi.org/10.1111/cns.12832

Abstract

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
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 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.

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.

Item Type:	Article
Identifier:	10.1111/cns.12832
Keywords:	Prostaglandin E2; hippocampus; neuroinflammation; postoperative cognitive dysfunction; synaptic plasticity-related protein
Subjects:	Medicine and health Psychology
Depositing User:	Anne Manyande
Date Deposited:	22 Feb 2018 18:26
Last Modified:	04 Nov 2024 12:03
URI:	https://repository.uwl.ac.uk/id/eprint/4442