Beal M F, Swartz K J, Isacson O
Neurochemistry Laboratory, Massachusetts General Hospital, Boston 02114.
Brain Res Dev Brain Res. 1992 Jul 24;68(1):136-9. doi: 10.1016/0165-3806(92)90256-v.
The cerebral distribution and regulation of excitatory amino acid levels may play a crucial role in neuronal development. In the present study we examined concentrations of the endogenous excitatory amino acid antagonist kynurenic acid and related substances during development in fetal and neonatal rat brain and fetal non-human primate cerebral cortex. Kynurenic acid concentrations in rat fetal whole brain were significantly increased 4-5 fold prenatally, then declined rapidly at 1 day after birth, and reached adult concentrations at 7 days after birth. L-Kynurenine concentrations were also markedly increased prior to birth and then declined to adult concentrations at 1 day after birth. L-Tryptophan was increased 3 fold before birth, and decreased to adult concentrations 1 day after birth. In contrast concentrations of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid and homovanillic acid increased 1 day prior to birth and continued to increase following birth. Fetal baboon cerebral cortex showed significant increases in kynurenic acid concentrations both pre-term and near-term as compared with adult concentrations. These results show that marked changes in kynurenic acid concentrations occur prior to and following birth. It is possible that high levels of kynurenic acid prior to birth inhibit neurite branching and development of excitatory synapses, which then develop rapidly in parallel with the decrease in kynurenic acid levels.
兴奋性氨基酸水平的脑部分布及调节可能在神经元发育中起关键作用。在本研究中，我们检测了胎鼠和新生鼠脑以及胎猴大脑皮质发育过程中内源性兴奋性氨基酸拮抗剂犬尿喹啉酸及相关物质的浓度。胎鼠全脑的犬尿喹啉酸浓度在出生前显著增加4至5倍，然后在出生后1天迅速下降，并在出生后7天达到成年浓度。L-犬尿氨酸浓度在出生前也显著增加，然后在出生后1天降至成年浓度。L-色氨酸在出生前增加3倍，并在出生后1天降至成年浓度。相比之下，多巴胺、去甲肾上腺素、3,4-二羟基苯乙酸和高香草酸的浓度在出生前1天增加，并在出生后持续增加。与成年浓度相比，早产和足月胎狒狒大脑皮质的犬尿喹啉酸浓度均显著增加。这些结果表明，犬尿喹啉酸浓度在出生前后发生显著变化。出生前高水平的犬尿喹啉酸可能会抑制神经突分支和兴奋性突触的发育，然后随着犬尿喹啉酸水平的下降而迅速发育。
