In:
CNS Neuroscience & Therapeutics, Wiley, Vol. 24, No. 10 ( 2018-10), p. 917-929
Kurzfassung:
Multifactors contribute to the development of postoperative cognitive dysfunction ( POCD ), of which the most important mechanism is neuroinflammation. Prostaglandin E2 ( PGE 2) is a key neuroinflammatory molecule and could modulate hippocampal synaptic transmission and plasticity. This study was designed to investigate whether PGE 2 and its receptors signaling pathway were involved in the pathophysiology of POCD . Methods Sixteen‐month old male C57 BL /6J mice were exposed to laparotomy. Cognitive function was evaluated by fear conditioning test. The levels of PGE 2 and its 4 distinct receptors ( EP 1‐4) were assessed by biochemical analysis. Pharmacological or genetic methods were further applied to investigate the role of the specific PGE 2 receptors. Results Here, we found that the transcription and translation level of the EP 3 receptor in hippocampus increased remarkably, but not EP 1, EP 2, or EP 4. Immunofluorescence results showed EP 3 positive cells in the hippocampal CA 1 region were mainly neurons. Furthermore, pharmacological blocking or genetic suppression of EP 3 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 PGE 2‐ EP 3 signaling pathway was involved in the progression of POCD and identified EP 3 receptor as a promising treatment target.
Materialart:
Online-Ressource
ISSN:
1755-5930
,
1755-5949
DOI:
10.1111/cns.2018.24.issue-10
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2018
ZDB Id:
2423467-9
