Developmental neurotoxicity: Do similar phenotypes indicate a common mode of action? A comparison of fetal alcohol syndrome, toluene embryopathy and maternal phenylketonuria

L. G. Costa, Marina Guizzetti, M. Burry, J. Oberdoerster

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Developmental neurotoxicity can be ascribed to in utero exposure to exogenous substances or to exposure of the fetus to endogenous compounds that accumulate because of genetic mutations. One of the best recognized human neuroteratogens is ethanol. The Fetal Alcohol Syndrome (FAS) is characterized by growth deficiency, particular facial features, and central nervous system (CNS) dysfunctions (mental retardation, microencephaly and brain malformations). Abuse of toluene by pregnant women can lead to an embryopathy (fetal solvent syndrome, (FSS)) whose characteristics are similar to FAS. Phenylketonuria (PKU) is a genetic defect in phenylalanine (Phe) metabolism. Offspring of phenylketonuric mothers not under strict dietary control are born with maternal PKU (mPKU), a syndrome with similar characteristics as FAS and FSS. While ethanol has been shown to cause neuronal death, no such evidence is available for toluene or Phe and/or its metabolites. On the other hand, alterations in astrocyte proliferation and maturation have been found, mostly in in vitro studies, which may represent a potential common mode of action for at least some of the CNS effects found in FAS, mPKU, and FSS. Further in vivo and in vitro studies should validate this hypothesis and elucidate possible molecular targets.

Original languageEnglish (US)
Pages (from-to)197-205
Number of pages9
JournalToxicology Letters
Volume127
Issue number1-3
DOIs
StatePublished - Feb 28 2002
Externally publishedYes

Fingerprint

Maternal Phenylketonuria
Fetal Alcohol Spectrum Disorders
Toluene
Alcohols
Phenotype
Neurology
Phenylalanine
Ethanol
Central Nervous System
Fetal Diseases
Phenylketonurias
Metabolites
Metabolism
Astrocytes
Intellectual Disability
Pregnant Women
Cause of Death
Brain
Fetus
Mothers

Keywords

  • Fetal alcohol syndrome
  • Glial cells
  • Maternal phenylketonuria
  • Neuronal death
  • Toluene embryopathy

ASJC Scopus subject areas

  • Toxicology

Cite this

Developmental neurotoxicity : Do similar phenotypes indicate a common mode of action? A comparison of fetal alcohol syndrome, toluene embryopathy and maternal phenylketonuria. / Costa, L. G.; Guizzetti, Marina; Burry, M.; Oberdoerster, J.

In: Toxicology Letters, Vol. 127, No. 1-3, 28.02.2002, p. 197-205.

Research output: Contribution to journalArticle

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