Persistent alterations in biomarkers of oxidative stress resulting from combined in utero and neonatal manganese inhalation

Keith M. Erikson, David C. Dorman, Lawrence H. Lash, Michael Aschner

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Neonatal female and male rats were exposed to airborne manganese sulfate (MnSO4) during gestation and postnatal d 1-18. Three weeks post-exposure, rats were killed and we assessed biochemical end points indicative of oxidative stress in five brain regions: cerebellum, hippocampus, hypothalamus, olfactory bulb, and striatum. Glutamine synthetase (GS) protein levels, metallothionein (MT) and GS mRNA levels, and total glutathione (GSH) levels were determined for all five regions. Overall, there was a statistically significant effect of manganese exposure on decreasing brain GS protein levels (p=0.0061), although only the highest dose of manganese (1 mg Mn/m3) caused a significant increase in GS messenger RNA (mRNA) in both the hypothalamus and olfactory bulb of male rats and a significant decrease in GS mRNA in the striatum of female rats. This highest dose of manganese had no effect on MT mRNA in either males or females; however, the lowest dose (0.05 mg Mn/m3) decreased MT mRNA in the hippocampus, hypothalamus, and striatum in males. The median dose (0.5 mg Mn/m3) led to decreased MT mRNA in the hippocampus and hypothalamus of the males and olfactory bulb of the females. Overall, manganese exposure did not affect total GSH levels, a finding that is contrary to those in our previous studies. Only the cerebellum of manganese-exposed young male rats showed a significant reduction (p<0.05) in total GSH levels compared to control levels. These data reveal that alterations in biomarkers of oxidative stress resulting from in utero and neonatal exposures of airborne manganese remain despite 3 wk of recovery; however, it is important to note that the doses of manganese utilized represent levels that are 100-fold to a 1000-fold higher than the inhalation reference concentration set by the US Environmental Protection Agency.

Original languageEnglish (US)
Pages (from-to)151-163
Number of pages13
JournalBiological Trace Element Research
Volume104
Issue number2
DOIs
StatePublished - May 1 2005
Externally publishedYes

Keywords

  • Brain
  • Glutamine synthetase
  • Glutathione
  • In utero
  • Manganese
  • Metallothionein
  • Rat

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical
  • Inorganic Chemistry

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