title: The effect of methylmercury exposure on behavior and cerebellar granule cell physiology in aged mice.
abstract: Epidemiology studies have clearly documented that the central nervous system is highly susceptible to methylmercury toxicity, and exposure to this neurotoxicant in humans primarily results from consumption of contaminated fish. While the effects of methylmercury exposure have been studied in great detail, comparatively little is known about the effects of moderate to low dose methylmercury toxicity in the aging central nervous system. We examined the toxic effects of a moderate dose of methylmercury on the aging mouse cerebellum. Male and female C57BL/6 mice at 16-20 months of age were exposed to methylmercury by feeding a total dose of 5.0 mg kg(-1) body weight and assessed using four behavioral tests. Methylmercury-treated aged mice performed significantly worse in open field, footprint analysis and the vertical pole test compared with age-matched control mice. Isolated cerebellar granule cells from methylmercury-treated aged mice exhibited higher levels of reactive oxygen species and reduced mitochondrial membrane potentials, but no differences in basal intracellular calcium ion levels compared with age-matched control mice. When aged mice were exposed to a moderate dose of methylmercury, they exhibited a similar degree of impairment when compared with young adult mice exposed to the same moderate dose of methylmercury, as reported in earlier studies from this laboratory. Thus, at least in mice, exposure of the aged brain to moderate concentrations methylmercury does not pose greater risk compared with the young adult brain exposed to similar concentrations of methylmercury.
authors.affiliation: Safety Assessment, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Sairam
authors.initials: S
authors.lastname: Bellum
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Thuett
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Bawa
authors.forename: Louise C
authors.initials: LC
authors.lastname: Abbott
mesh_terms: D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D008767:Methylmercury Compounds; D017382:Reactive Oxygen Species; D002118:Calcium