Whittle Nigel, Sartori Simone B, Dierssen Mara, Lubec Gert, Singewald Nicolas
Department of Pharmacology and Toxicology, Institute of Pharmacy and Center for Molecular Biosciences, University of Innsbruck, Innsbruck, Austria.
Pediatrics. 2007 Dec;120(6):e1465-71. doi: 10.1542/peds.2006-3448. Epub 2007 Nov 12.
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.
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 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.
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.
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.
在未成熟的胎儿大脑发育过程中，氨基酸（如γ-氨基丁酸和牛磺酸）和单胺（血清素、去甲肾上腺素和多巴胺）起着发育信号或调节因子的作用。在唐氏综合征患者中，从出生起就明显存在大脑发育功能障碍，表现为脑重量减轻，特定脑区体积减小，且观察到神经元、树突和树突分支数量改变。然而，唐氏综合征中观察到的大脑发育功能障碍的潜在机制尚不清楚。
由于多种氨基酸和单胺对正常大脑发育至关重要，我们想确定唐氏综合征患者中观察到的大脑发育功能障碍是否与大脑氨基酸和/或单胺水平改变有关。
设计/方法：我们对妊娠约20周的唐氏综合征胎儿组织与年龄匹配的对照流产胎儿额叶皮质中多种氨基酸（包括γ-氨基丁酸和牛磺酸）以及单胺血清素、去甲肾上腺素和多巴胺的组织浓度进行了定量分析。
唐氏综合征胎儿大脑额叶皮质中的血清素、γ-氨基丁酸、牛磺酸和多巴胺水平降低。未观察到精氨酸、天冬氨酸、谷氨酰胺、谷氨酸、甘氨酸、组氨酸、丝氨酸或去甲肾上腺素水平的改变。
血清素、γ-氨基丁酸、牛磺酸和多巴胺对大脑形态特征的获得、神经元和神经胶质细胞的增殖以及突触形成至关重要。这些神经递质水平的检测到的降低可能表明唐氏综合征胎儿大脑中观察到的神经元发育功能障碍的潜在机制。
