Effects Of ?-Opioid Receptor In Epilepsy Induced By Pentylenetetrazol

Epilepsy,a chronic neurodegenerative disease,has very detrimental effects on the body and mental of patients.?-opioid receptor is an important G protein-coupled receptor in the central nervous system,which has neuroprotective effects and is closely related to epilepsy.In this paper,we investigated the relationship between ?-opioid receptor and the development of epilepsy,as well as the possible mechanism of ?-opioid receptor in epilepsy.In this study,we established an animal model by pentylenetetrazol.?-opioid receptor agonist DADLE and antagonist naltrexone were used to regulated the activity of ?-opioid receptor,when carbamazepine was used as a positive drug.After administration,the behavior of mice was analyzed considering Racine grading criteria.We found that DADLE could prolong the latency of seizures and reduce the severity of seizures,while naltrexone aggravated epileptic seizures.The stain results showed that DADLE could alleviate neuronal damage while naltrexone could aggravate neuronal injury,indicating that activation of ?-opioid receptors might have a protective role in epilepsy.DADLE also inhibited the up-regulation of interleukin-1? in epileptic mice.In addition,the western blot results showed that pentylenetetrazol up-regulated the expression of ?-opioid receptors in cortical but not in hippocampus.DADLE will further stimulate the expression of ?-opioid receptors.And the phosphorylation of ERK was inhibited by DADLE in mice cortical.Then we explored the mechanism of ?-opioid receptor in epilepsy induced by pentylenetetrazol.We used neuronal pheochromocytoma cells to study the protective effects of?-opioid receptors and the role of BDNF-ERK pathways during this process.Cells were treated with different levels of pentylenetetrazol and DADLE.Methyl thiazolyl tetrazolium assay and test for extracellular lactic dehydrogenase level showed that DADLE alleviated the damage of cells.And DADLE influenced a boost in ?-opioid receptors protein.To analyze the relationship between BDNF-ERK and ?-opioid receptors,we found that DADLE increased the level of BDNF significantly while naltrexone decreased the level of BDNF.At the same time,blocking the BDNF/TrkB pathway by k252a,the effects of DADLE on superoxide dismutase activity and glutathione content was inhibited.Results also showed that pentylenetetrazol increased the phosphorylation of ERK in a short time,but ?-opioid receptors interfering with DADLE or naltrexone had no significant effect on the phosphorylation of ERK.The above results show that activation of ?-opioid receptors could inhibit seizures and play a neuroprotective role in seizures.The protective effects may be related to the up-regulation of ?-opioid receptors.In addition,the BDNF/TrkB signaling pathway may be involved in the effects of 5-opioid receptor in epilepsy.However,further research is needed to find out whether ERK is related to the regulation of 5-opioid receptor.