title: Exploring cross-talk between oxidative damage and excitotoxicity and the effects of riluzole in the rat cortex after exposure to methylmercury.
abstract: Methylmercury (MeHg) is a ubiquitous environmental toxin that causes neurologic and developmental diseases. Oxidative damage and excitotoxicity are putative mechanisms, which underlie MeHg-induced neurotoxicity. In this study, the cross-talk between the oxidative damage and excitotoxicity pathways and the protective effects of riluzole in the rat cortex were explored. Rats were injected with MeHg and/or riluzole, and cold vapor atomic fluorescence spectrometry, hematoxylin and eosin staining, flow cytometry, fluorescence assays, spectrophotometry, real-time PCR, and Western blotting were used to evaluate neurotoxicity. The present study showed that (1) MeHg accumulated in the cerebral cortex and caused pathology. (2) MeHg caused oxidative damage by inducing glutathione (GSH) depletion, reactive oxygen species (ROS) production, inhibition of antioxidant enzyme activity, and alteration of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. (3) MeHg disrupted the glutamate transporters (GluTs), glutamate-glutamine cycle, and N-methyl-D-aspartate receptor expression and induced excitotoxicity. (4) Excitotoxicity resulted in disruption of GSH synthesis, calcium overloading, oxidative damage, and excessive ROS production. (5) Pretreatment with riluzole antagonized MeHg neurotoxicity by down regulating cross-talk between the oxidative damage and excitotoxicity pathways. In conclusion, the cross-talk between the oxidative damage and excitotoxicity pathways caused by MeHg exposure was linked by GluTs and calcium and inhibited by riluzole treatment.
authors: Department of Environmental Health, School of Public Health, China Medical University, North 2nd Road 92, Heping Ward, Shenyang, 110001, Liaoning, People's Republic of China, dengyu.cmu@163.com.
authors: Yu
authors: Y
authors: Deng
authors: Zhaofa
authors: Z
authors: Xu
authors: Bin
authors: B
authors: Xu
authors: Wei
authors: W
authors: Liu
authors: Yangang
authors: Y
authors: Wei
authors: Yuehui
authors: Y
authors: Li
authors: Shu
authors: S
authors: Feng
authors: Tianyao
authors: T
authors: Yang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008628:Mercury / Q000378:metabolism; D008767:Methylmercury Compounds / Q000633:toxicity*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D019782:Riluzole / Q000494:pharmacology*
chemical_list: D050491:Glutamate Plasma Membrane Transport Proteins; D008767:Methylmercury Compounds; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D009498:Neurotoxins; C495637:Nfe2l2 protein, rat; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D005973:Glutamine; D018698:Glutamic Acid; D019782:Riluzole; D008628:Mercury; D005978:Glutathione; D002118:Calcium