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Neurotoxic effects of postnatal thimerosal are mouse strain dependent

Abstract

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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Acknowledgements

This work was supported by grants from UC Davis M.I.N.D. Institute (MH), Coalition for Safe Minds (MH), The Ellison Medical Foundation (WIL), and NIH HD37546 (WIL). The technical assistance of Janelle Villiers, Arya Soman, and Peter Hardigan is gratefully acknowledged.

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Hornig, M., Chian, D. & Lipkin, W. Neurotoxic effects of postnatal thimerosal are mouse strain dependent. Mol Psychiatry 9, 833–845 (2004). https://doi.org/10.1038/sj.mp.4001529

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Keywords

  • autistic disorder
  • thimerosal
  • neurotoxicity
  • autoimmunity
  • inbred mouse strains

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