title: The effects of methylmercury exposure on behavior and biomarkers of oxidative stress in adult mice.
abstract: Methylmercury (MeHg) is a widely distributed environmental neurotoxin with established effects on locomotor behaviors and cognition in both human populations and animal models. Despite well-described neurobehavioral effects, the mechanisms of MeHg toxicity are not completely understood. Previous research supports a role for oxidative stress in the toxic effects of MeHg. However, comparing findings across studies has been challenging due to differences in species, methodologies (in vivo or in vitro studies), dosing regimens (acute vs. long-term) and developmental life stage. The current studies assess the behavioral effects of MeHg in adult mice in conjunction with biochemical and cellular indicators of oxidative stress using a consistent dosing regimen. In Experiment 1, adult male C57/BL6 mice were orally administered 5 mg/kg/day MeHg or the vehicle for 28 days. Impact of MeHg exposure was assessed on inverted screen and Rotor-Rod behaviors as well as on biomarkers of oxidative stress (thioredoxin reductase (TrxR), glutathione reductase (GR) and glutathione peroxidase (GPx)) in brain and liver. In Experiment 2, brain tissue was immunohistochemically labeled for 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidation and an indicator of oxidative stress, following the same dosing regimen. 8-OHdG immunoreactivity was measured in the motor cortex, the magnocellular red nucleus (RMC) and the accessory oculomotor nucleus (MA3). Significant impairments were observed in MeHg-treated animals on locomotor behaviors. TrxR and GPx was significantly inhibited in brain and liver, whereas GR activity decreased in liver and increased in brain tissue of MeHg-treated animals. Significant MeHg-induced alterations in DNA oxidation were observed in the motor cortex, the RMC and the MA3.
authors.affiliation: Psychology Department and Neuroscience Program, Wheaton College, 26 East Main Street, Norton, MA 02766, United States. Electronic address: Kirkpatrick_meg@wheatoncollege.edu.
authors.forename: Meg
authors.initials: M
authors.lastname: Kirkpatrick
authors.affiliation: Chemistry Department, Wheaton College, United States.
authors.forename: Janina
authors.initials: J
authors.lastname: Benoit
authors.affiliation: Psychology Department and Neuroscience Program, Wheaton College, 26 East Main Street, Norton, MA 02766, United States.
authors.forename: Wyll
authors.initials: W
authors.lastname: Everett
authors.affiliation: Psychology Department and Neuroscience Program, Wheaton College, 26 East Main Street, Norton, MA 02766, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gibson
authors.affiliation: Chemistry Department, Wheaton College, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Rist
authors.affiliation: Chemistry Department, Wheaton College, United States.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Fredette
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D009044:Motor Cortex / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects*; D013879:Thioredoxins / Q000378:metabolism; D013997:Time Factors
chemical_list: D008767:Methylmercury Compounds; D013879:Thioredoxins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D003849:Deoxyguanosine; D005978:Glutathione
keywords: 8-OHdG; Locomotor behavior; Methylmercury; Neurotoxicity; Oxidative stress