TY - JOUR
T1 - Developmental neurotoxicity
T2 - Do similar phenotypes indicate a common mode of action? A comparison of fetal alcohol syndrome, toluene embryopathy and maternal phenylketonuria
AU - Costa, L. G.
AU - Guizzetti, M.
AU - Burry, M.
AU - Oberdoerster, J.
N1 - Funding Information:
Research by the authors was supported by grants from the National Institutes of Health (ES-07033, ES-10120, AA-08154), and the European Union (QLK4-1999-01562).
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Fetal alcohol syndrome
KW - Glial cells
KW - Maternal phenylketonuria
KW - Neuronal death
KW - Toluene embryopathy
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U2 - 10.1016/S0378-4274(01)00501-X
DO - 10.1016/S0378-4274(01)00501-X
M3 - Article
C2 - 12052659
AN - SCOPUS:0037186908
SN - 0378-4274
VL - 127
SP - 197
EP - 205
JO - Toxicology Letters
JF - Toxicology Letters
IS - 1-3
M1 - 4974
ER -