Speciale C, Okuno E, Schwarcz R
Maryland Psychiatric Research Center, Baltimore 21228.
Brain Res. 1987 Dec 8;436(1):18-24. doi: 10.1016/0006-8993(87)91551-4.
The excitotoxic brain metabolite quinolinic acid (QUIN) has been hypothetically linked to the pathogenesis of seizure disorders and other neurodegenerative events affecting the hippocampal formation. Its biosynthetic enzyme, 3-hydroxyanthranilic acid oxygenase (3-HAO) and its catabolic enzyme, quinolinic acid phosphoribosyltransferase (QPRT), can be used as markers for the cellular localization of the brain's QUIN system. Measured between 2 days and 2 months following intrahippocampal ibotenic acid injections, the activities of both enzymes increased at the lesion site due to the synthesis of new enzyme protein. The time course of the increase in 3-HAO activity coincided with that of the known astrocytic proliferation following excitotoxic insults. It is less obvious if the elevation in QPRT activity, too, is related to an increase in the number of reactive glial cells. No changes in the activity of hippocampal 3-HAO or QPRT were noted 7 or 60 days after cholinergic deafferentation by fornix-fimbria transection nor were any changes observed in the contralateral hippocampus at any time-point following the ibotenate lesion. These data raise the possibility that a feed-forward mechanism, resulting in ever increasing amounts of QUIN in the brain, may be operant in situations of progressive hippocampal nerve cell loss.
兴奋性毒性脑代谢物喹啉酸（QUIN）被推测与癫痫发作性疾病以及其他影响海马结构的神经退行性病变的发病机制有关。其生物合成酶3-羟基邻氨基苯甲酸加氧酶（3-HAO）及其分解代谢酶喹啉酸磷酸核糖基转移酶（QPRT），可用作大脑QUIN系统细胞定位的标志物。在海马内注射鹅膏蕈氨酸后2天至2个月期间测量，由于新酶蛋白的合成，两种酶的活性在损伤部位均增加。3-HAO活性增加的时间进程与兴奋性毒性损伤后已知的星形胶质细胞增殖的时间进程一致。QPRT活性的升高是否也与反应性神经胶质细胞数量的增加有关则不太明显。穹窿-海马伞横断致胆碱能去传入后7天或60天，海马3-HAO或QPRT的活性未发现变化，在鹅膏蕈氨酸损伤后的任何时间点，对侧海马也未观察到任何变化。这些数据提出了一种可能性，即在进行性海马神经细胞丢失的情况下，可能存在一种前馈机制，导致大脑中QUIN的量不断增加。
