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

View Article: PubMed Central - PubMed

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 dose-dependent 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-EP1-4 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.

No MeSH data available.


Related in: MedlinePlus

Protection of hippocampus neurons from aluminum-overload injury by misoprostol in rats. Arrow indicates karyopyknosis of nerve cells. Dead nerve cell is identified by eosinophilic change including neuron became a red and deep cell with nucleoli disappear under light microscope. #P<0.05 and ##P<0.01 compared with control group, *P<0.05 and **P<0.01 compared with Al-overload group (Data are reported as mean ± SD. n=4).
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Figure 1: Protection of hippocampus neurons from aluminum-overload injury by misoprostol in rats. Arrow indicates karyopyknosis of nerve cells. Dead nerve cell is identified by eosinophilic change including neuron became a red and deep cell with nucleoli disappear under light microscope. #P<0.05 and ##P<0.01 compared with control group, *P<0.05 and **P<0.01 compared with Al-overload group (Data are reported as mean ± SD. n=4).

Mentions: In the control group, the hippocampus neurons were regularly structured and closely arranged, and the morphological structure was intact and clear. By comparison, the Al-overload group showed significant injuries with remarkable karyopyknosis and cell loss. Administration of misoprostol dose-dependently reduced the neuronal pathomorphology in the aluminum-overload rats (Fig. 1).


Misoprostol Reverse Hippocampal Neuron Cyclooxygenase-2 Downstream Signaling Imbalance in Aluminum-Overload Rats
Protection of hippocampus neurons from aluminum-overload injury by misoprostol in rats. Arrow indicates karyopyknosis of nerve cells. Dead nerve cell is identified by eosinophilic change including neuron became a red and deep cell with nucleoli disappear under light microscope. #P<0.05 and ##P<0.01 compared with control group, *P<0.05 and **P<0.01 compared with Al-overload group (Data are reported as mean ± SD. n=4).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4997938&req=5

Figure 1: Protection of hippocampus neurons from aluminum-overload injury by misoprostol in rats. Arrow indicates karyopyknosis of nerve cells. Dead nerve cell is identified by eosinophilic change including neuron became a red and deep cell with nucleoli disappear under light microscope. #P<0.05 and ##P<0.01 compared with control group, *P<0.05 and **P<0.01 compared with Al-overload group (Data are reported as mean ± SD. n=4).
Mentions: In the control group, the hippocampus neurons were regularly structured and closely arranged, and the morphological structure was intact and clear. By comparison, the Al-overload group showed significant injuries with remarkable karyopyknosis and cell loss. Administration of misoprostol dose-dependently reduced the neuronal pathomorphology in the aluminum-overload rats (Fig. 1).

View Article: PubMed Central - PubMed

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 dose-dependent 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-EP1-4 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.

No MeSH data available.


Related in: MedlinePlus