Fetal Down syndrome brains exhibit aberrant levels of neurotransmitters critical for normal brain development.
BACKGROUND
In the immature developing fetal brain, amino acids (such as gamma-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.


OBJECTIVE
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.


METHODS
We quantified tissue concentrations of diverse amino acids, including gamma-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 approximately 20 weeks versus age-matched control aborted fetuses.


RESULTS
Fetal Down syndrome brains showed reductions in the levels of serotonin, gamma-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, gamma-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.
Whittle
Nigel
N
Department of Pharmacology and Toxicology, Institute of Pharmacy and Center for Molecular Biosciences, University of Innsbruck, Innsbruck, Austria.
Sartori
Simone B
SB
Dierssen
Mara
M
Lubec
Gert
G
Singewald
Nicolas
N
D000596:Amino Acids / Q000032:analysis; D001921:Brain / Q000196:embryology*; D001923:Brain Chemistry; D002395:Catecholamines / Q000032:analysis; D004314:Down Syndrome / Q000196:embryology*; D005625:Frontal Lobe / Q000737:chemistry; D006801:Humans; D008297:Male; D018377:Neurotransmitter Agents / Q000032:analysis*; D012701:Serotonin / Q000032:analysis
D000596:Amino Acids; D002395:Catecholamines; D018377:Neurotransmitter Agents; D012701:Serotonin