Cultured lymphocytes from autistic children and non-autistic siblings up-regulate heat shock protein RNA in response to thimerosal challenge

Stephen J. Walker, Jeffrey Segal, Michael Aschner

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

There are reports suggesting that some autistic children are unable to mount an adequate response following exposure to environmental toxins. This potential deficit, coupled with the similarity in clinical presentations of autism and some heavy metal toxicities, has led to the suggestion that heavy metal poisoning might play a role in the etiology of autism in uniquely susceptible individuals. Thimerosal, an anti-microbial preservative previously added routinely to childhood multi-dose vaccines, is composed of 49.6% ethyl mercury. Based on the levels of this toxin that children receive through routine immunization schedules in the first years of life, it has been postulated that thimerosal may be a potential triggering mechanism contributing to autism in susceptible individuals. One potential risk factor in these individuals may be an inability to adequately up-regulate metallothionein (MT) biosynthesis in response to presentation of a heavy metal challenge. To investigate this hypothesis, cultured lymphocytes (obtained from the Autism Genetic Resource Exchange, AGRE) from autistic children and non-autistic siblings were challenged with either 10 μM ethyl mercury, 150 μM zinc, or fresh media (control). Following the challenge, total RNA was extracted and used to query "whole genome" DNA microarrays. Cultured lymphocytes challenged with zinc responded with an impressive up-regulation of MT transcripts (at least nine different MTs were over-expressed) while cells challenged with thimerosal responded by up-regulating numerous heat shock protein transcripts, but not MTs. Although there were no apparent differences between autistic and non-autistic sibling responses in this very small sampling group, the differences in expression profiles between those cells treated with zinc versus thimerosal were dramatic. Determining cellular response, at the level of gene expression, has important implications for the understanding and treatment of conditions that result from exposure to neurotoxic compounds.

Original languageEnglish (US)
Pages (from-to)685-692
Number of pages8
JournalNeuroToxicology
Volume27
Issue number5
DOIs
StatePublished - Sep 2006
Externally publishedYes

Fingerprint

Thimerosal
Lymphocytes
Autistic Disorder
Heat-Shock Proteins
Siblings
Up-Regulation
Heavy Metals
RNA
Zinc
Metallothionein
Mercury
Immunization Schedule
Immunization
Biosynthesis
Environmental Exposure
Microarrays
Oligonucleotide Array Sequence Analysis
Gene expression
Toxicity
Vaccines

Keywords

  • Autism
  • Ethyl mercury
  • Metallothionein
  • Micorarrays

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neuroscience(all)
  • Toxicology

Cite this

Cultured lymphocytes from autistic children and non-autistic siblings up-regulate heat shock protein RNA in response to thimerosal challenge. / Walker, Stephen J.; Segal, Jeffrey; Aschner, Michael.

In: NeuroToxicology, Vol. 27, No. 5, 09.2006, p. 685-692.

Research output: Contribution to journalArticle

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