Misoprostol Reverse Hippocampal Neuron Cyclooxygenase-2 Downstream Signaling Imbalance in Aluminum-Overload Rats

Title:Misoprostol Reverse Hippocampal Neuron Cyclooxygenase-2 Downstream Signaling Imbalance in Aluminum-Overload Rats

Volume: 13 Issue: 9

Author(s): Yuanxin Guo, Wenjuan Lei, Jianfeng Wang, Xinyue Hu, Yuling Wei, Chaonan Ji and Junqing Yang*

Affiliation:

• Department of Pharmacology, Chongqing Medical University, Chongqing 400016,China

Keywords: Alzheimer disease , neurodegeneration, misoprostol, PGE₂, PGES, EPs receptor.

Abstract: Although COX-2 inhibition in animal models of neurodegenerative diseases has shown neuroprotection, recent studies have revealed some serious side effects (ulcers, bleeding, fatal cerebrovascular diseases etc.) and the limited benefits of COX-2 inhibitors. A more focused approach is necessary to explore the therapeutic effect of the COX downstream signaling pathway in neurological research. The aim of this study was to explore the alterations of the PGES-PGE₂-EP signal pathway and the effect of misoprostol on neurodegeneration by chronic aluminum-overload in rats. Adult rats were treated by intragastric administration of aluminum gluconate. The PGE₂ content and expression of PGES and EPs in the hippocampi of rats were detected using ELISA, q-PCR and Western blot analysis, respectively. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the rat hippocampi were also detected. The misoprostol treatment dose-dependently improved spatial learning and memory function as well as healing after hippocampal neuron damage induced by chronic aluminum-overload in rats. Meanwhile, the administration of misoprostol resulted in a decrease in the PGE2 level and down-regulation of the mPGES-1, EP₂ and EP₄ expression levels, while there was a dosedependent up-regulation of EP3 expression. These results suggest that misoprostol possesses a neuroprotective property, and the mechanism involves affecting the EP3 level and reducing the endogenous production of PGE₂ through a negative feedback mechanism, increasing the EP₃ expression level, decreasing the EP₂ and EP₄ expression levels, and rebuilding the mPGES-1-PGE₂-EP_1-4 signal pathway balance. In this way, misoprostol has a counteractive effect on oxidant stress and inflammation in the central nervous system. The PGES-PGE2-EPs signaling pathway is a potential therapeutic strategy for treating neurodegeneration in patients.

Cite this article as:

Guo Yuanxin, Lei Wenjuan, Wang Jianfeng, Hu Xinyue, Wei Yuling, Ji Chaonan and Yang Junqing*, Misoprostol Reverse Hippocampal Neuron Cyclooxygenase-2 Downstream Signaling Imbalance in Aluminum-Overload Rats, Current Alzheimer Research 2016; 13 (9) . https://dx.doi.org/10.2174/1567205013666160401114601