Neurotoxicity and immunotoxicity assessment in CBA/J mice with chronic Toxoplasma gondii infection and single-dose exposure to methylmercury.
Toxoplasma gondii is a protozoan parasite that localizes in the brain where it can cause life-threatening disease. Methylmercury (MeHg) is a well-documented neurotoxicant that accumulates in the brain. We investigated end points associated with immunotoxicity and neurotoxicity in mice exposed to MeHg during a chronic T. gondii infection. Two groups of 6-week-old, female CBA/J mice were either fed 25 T. gondii tissue cysts of the ME-49 strain or given vehicle. Six weeks later, half of the mice in each group were orally gavaged with a single dose of 20 mg/kg body weight of MeHg, creating four groups of mice (vehicle control, T. gondii, MeHg, and T. gondii/MeHg). Mice were sacrificed 7 days post MeHg exposure. MeHg exposure caused a significant decrease in mouse body weight. MeHg administration resulted in an increase of splenic cellularity and spleen-to-body weight ratios. MeHg had no significant effect on the percentages of CD4(+), CD8(+), or non-T-cell subpopulations in the spleen. MeHg dosed mice demonstrated an increase in absolute numbers of splenic CD4(+), CD8(+), or non-T cells when compared to mice in control and T. gondii-infected groups. Thymic CD4(+)CD8(+) T-cell subpopulations were decreased (p <.05) by MeHg with or without a concurrent T. gondii infection. There was a significant (p <.05) increase in brain tissue cyst counts within the group exposed to both MeHg and T. gondii (16 +/- 4, mean +/- SE, n = 7) versus T. gondii alone (4 +/- 1, n = 8). Histopathological examination demonstrated encephalitis, gliosis, and meningitis in brains from mice infected with T. gondii. These data indicate that exposure to both MeHg and T. gondii has synergistic effects, with effects of MeHg especially on the immune system.
King
Marquea D
MD
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061-0442, USA. marion@vt.edu
Lindsay
David S
DS
Holladay
Steven
S
Ehrich
Marion
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000469:parasitology / Q000473:pathology; D002908:Chronic Disease; D004357:Drug Synergism; D005260:Female; D008221:Lymphoid Tissue / Q000187:drug effects / Q000473:pathology; D008767:Methylmercury Compounds / Q000276:immunology / Q000633:toxicity*; D051379:Mice; D008808:Mice, Inbred CBA; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology; D014122:Toxoplasma / Q000254:growth & development; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000469:parasitology
D008767:Methylmercury Compounds