title: MK-801 protects against intracellular Ca(2+) overloading and improves N-methyl-D-aspartate receptor expression in cerebral cortex of methylmercury-poisoned rats.
abstract: Overexposure to methylmercury (MeHg) has been known to induce neurotoxicity. The objective of this study is to explore mechanisms that contribute to MeHg-induced nerve cell apoptosis focusing on the alteration of intracellular Ca(2+) homeostasis and expression of N-methyl-D-aspartate receptors (NMDARs) subunits in rat cerebral cortex and whether MK801, a non-competitive NMDAR antagonist, could attenuate MeHg-induced neurotoxicity. Fifty rats were randomly divided into five groups of 10 animals in each group: control group, MK801 control group, MeHg-treated group (4 and 12 μmol/kg) and MK801 pre-treated group. Administration of MeHg at a dose of 12 μmol/kg for 4 weeks significantly increased in intracellular [Ca(2+)](i) and total Hg levels and that enhanced neurocyte apoptosis rate in cerebral cortex. In addition, the inhibitory effect of MeHg on Na(+)-K(+)-ATPase and Ca(2+)-ATPases might be one of the reasons that cause a significant increase of [Ca(2+)](i) in neurocyte. Over activated by increased cytosolic Ca(2+) loading, calpains degraded NMDAR subunits leading ultimately to nerve cell damage. However, pretreatment with MK801 at a dose of 0.3 μmol/kg could prevent Ca(2+) homeostasis dysregulation and alleviate the neurocyte apoptosis. In conclusion, the neuroprotective effects of MK801 appeared to be mediated not only via its NMDA receptor binding properties but also by maintaining intracellular calcium homeostasis.
authors.affiliation: Department of Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning 110001, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Zhaofa
authors.initials: Z
authors.lastname: Xu
authors.forename: Yu
authors.initials: Y
authors.lastname: Deng
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Haibo
authors.initials: H
authors.lastname: Yang
authors.forename: Yan-Gang
authors.initials: YG
authors.lastname: Wei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002154:Calpain / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects; D008767:Methylmercury Compounds / Q000506:poisoning*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D008767:Methylmercury Compounds; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D002154:Calpain; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; C004925:methylmercuric chloride; D002118:Calcium