Effect of high dietary manganese intake of neonatal rats on tissue mineral accumulation, striatal dopamine levels, and neurodevelopmental status

Trinh T. Tran, Winyoo Chowanadisai, Francis M. Crinella, Aleksandra Chicz-DeMet, Bo Lönnerdal

Research output: Contribution to journalArticle

73 Scopus citations


Mn is an essential element, but may become neurotoxic at high levels. Recent reports of high Mn levels in hair of children with neurodevelopmental deficits suggest that these deficits could be due to Mn-induced neurotoxic effects on brain dopamine (DA) systems, although the mechanism is not well understood. Infant formulas contain considerably higher concentrations of Mn than human milk. Thus, formula-fed infants are exposed to high levels of Mn at a time when Mn homeostasis is incompletely developed. We studied the effects of dietary Mn supplementation of rat pups on tissue Mn accumulation, brain dopamine levels, infant neurodevelopmental status, and behavior at maturity. Newborn rats were supplemented daily with 0, 50, 250, or 500 μg Mn given orally from day 1 to day 20. Mineral analysis of small intestine and brain at day 14 showed a significant increase of tissue Mn in supplemented rats. Neurodevelopmental tests conducted at various ages showed significant delays as a function of Mn supplementation. At day 32, there was a significant positive relationship between passive avoidance errors and Mn supplementation levels. Brains of animals killed on day 40 showed a significant inverse relationship between Mn supplementation level and striatal dopamine concentration. These observations suggest that dietary exposure to high levels of Mn during infancy can be neurotoxic to rat pups and result in developmental deficits.

Original languageEnglish (US)
Pages (from-to)635-643
Number of pages9
Issue number4-5
StatePublished - Oct 2002



  • Behavior
  • Dopamine
  • Infants
  • Manganese
  • Trace minerals

ASJC Scopus subject areas

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

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