PEDIATRICS Vol. 120 No. 6 December 2007, pp. e1465-e1471 (doi:10.1542/peds.2006-3448)
ARTICLE |
Fetal Down Syndrome Brains Exhibit Aberrant Levels of Neurotransmitters Critical for Normal Brain Development
a Department of Pharmacology and Toxicology, Institute of Pharmacy and Center for Molecular Biosciences, University of Innsbruck, Innsbruck, Austria
b Neurobehavioral Analysis Laboratory, Genes and Disease Program, Center for Genomic Regulation, Barcelona, Spain and Centre for Biomedical Research on Rare Diseases (CIBERER), Barcelona, Spain
c Department of Pediatrics, Division of Basic Sciences, University of Vienna, Vienna, Austria
BACKGROUND. In the immature developing fetal brain, amino acids (such as 
-aminobutyric acid, and taurine) and monoamines (serotonin, noradrenaline, and dopamine) act as developmental signals or regulators. In subjects with Down syndrome, dysfunctional brain development is evident from birth as reduction in brain weight, as well as volume reductions in specific brain regions, and an altered number of neurons, dendrites, and dendritic branching is observed. However, mechanisms that underlie the observed dysfunctional brain development in Down syndrome are not clear.
OBJECTIVES. Because diverse amino acids and monoamines are critical for normal brain development, we wanted to determine whether dysfunctional brain development observed in subjects with Down syndrome is associated with altered brain amino acid and/or monoamine levels.
DESIGN/METHODS. We quantified tissue concentrations of diverse amino acids, including -aminobutyric acid and taurine, and the monoamines serotonin, noradrenaline, and dopamine in the frontal cortex of fetal Down syndrome tissue at a gestational age of 
20 weeks versus age-matched control aborted fetuses.
RESULTS. Fetal Down syndrome brains showed reductions in the levels of serotonin, -aminobutyric acid, taurine, and dopamine in the frontal cortex. No alteration in the levels of arginine, aspartate, glutamine, glutamate, glycine, histidine, serine, or noradrenaline was observed.
CONCLUSIONS. Serotonin, -aminobutyric acid, taurine, and dopamine are critical for the acquisition of brain morphologic features, neuronal and glia proliferation, and synapse formation. The detected reductions in the levels of these neurotransmitters may indicate potential mechanisms for the observed dysfunctional neuronal development in the Down syndrome fetal brain.
Key Words: Down syndrome • fetal • frontal cortex • brain development • serotonin • catecholamines • dopamine • amino acids • GABA • taurine
Abbreviations: CNS—central nervous system • GABA—-aminobutyric acid • DS—Down syndrome
Accepted May 14, 2007.
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