Neurotoxic effects of postnatal thimerosal are mouse strain dependent.
The developing brain is uniquely susceptible to the neurotoxic hazard posed by mercurials. Host differences in maturation, metabolism, nutrition, sex, and autoimmunity influence outcomes. How population-based variability affects the safety of the ethylmercury-containing vaccine preservative, thimerosal, is unknown. Reported increases in the prevalence of autism, a highly heritable neuropsychiatric condition, are intensifying public focus on environmental exposures such as thimerosal. Immune profiles and family history in autism are frequently consistent with autoimmunity. We hypothesized that autoimmune propensity influences outcomes in mice following thimerosal challenges that mimic routine childhood immunizations. Autoimmune disease-sensitive SJL/J mice showed growth delay; reduced locomotion; exaggerated response to novelty; and densely packed, hyperchromic hippocampal neurons with altered glutamate receptors and transporters. Strains resistant to autoimmunity, C57BL/6J and BALB/cJ, were not susceptible. These findings implicate genetic influences and provide a model for investigating thimerosal-related neurotoxicity.
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Jerome L and Dawn Greene Infectious Disease Laboratory, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032, USA. mady.hornig@columbia.edu
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Lipkin
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D000818:Animals; D001321:Autistic Disorder / Q000139:chemically induced* / Q000235:genetics; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000235:genetics*; D001522:Behavior, Animal / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D006130:Growth Disorders / Q000139:chemically induced; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D011310:Preservatives, Pharmaceutical / Q000633:toxicity*; D012737:Sex Factors; D013045:Species Specificity; D018709:Statistics, Nonparametric; D013849:Thimerosal / Q000633:toxicity*; D014612:Vaccines / Q000633:toxicity
D009498:Neurotoxins; D011310:Preservatives, Pharmaceutical; D014612:Vaccines; D013849:Thimerosal; D018698:Glutamic Acid