Analysis of encephalon physiological activator metabolic error mouse and development of brain function protective diet

喹啉酸(QA)被认为是阿尔茨海默氏症和帕金森氏病患者的病原体，因为他们的大脑中有大量的蓄积。敲除了喹啉磷酸核糖基转移酶基因的小鼠，是QA代谢的唯一酶，即内源性神经毒素，计划在2004财年初完成研究，因为它成功地制造了嵌合体小鼠。但是，F0小鼠并没有出生。然后，当过量使用增加QA或色氨酸生成量的化学物质时，检测Trp代谢。在这项研究中，使用了大鼠，因为色氨酸的代谢是众所周知的，我检查了非典型行为等的身体影响是否发生了QA的积累。ACMSD抑制剂吡津酰胺和邻苯二甲酸二乙基己酯可累积QA。加入这些药物后，QA的产量显着增加，既没有看到异常行为，也没有看到痉挛等身体影响。为了解大鼠体内色氨酸的代谢能力，检测了色氨酸-QA代谢中间产物的变化。结果表明，当饲料中添加5%色氨酸时，大鼠仍能将色氨酸代谢为3-羟基邻氨基苯甲酸。添加2%Trp时，QA产量增加，而添加2%和5%Trp时，QA产量增加不明显。通过3-HA-→QA反应，认为摄取2%色氨酸加日粮的色氨酸已达到饱和。提示QA在肝脏中形成的保护机制不能在脑中发挥作用。因此，当大脑中的QA增加到1000倍或更多时，这种保护机制的断裂似乎是导致疾病发展的根本原因。

The quinolinic acid (QA) is thought to be a causative agent of Alzheimer and Parkinson's disease patient's because of a lot of accumulation in their encephalons. The mouse that had knocked out the quinolinate phosphoribosyltransferase gene that was the only enzyme for the metabolism of QA that was the endogenous neurotoxin was scheduled to complete the research by the beginning in 2004 fiscal year, because it had succeeded in making of the chimaeric mouse. But, the F_0 mouse was not born. Then, the Trp metabolism when chemicals that increased the amount of the formation of QA or tryptophan were excessively administered was examined. In this research, rats were used because the metabolism of Trp was well known and I examined whether a body influence of atypical behavior etc. happened or not by the accumulation of QA. The QA was accumulated by the administration of the inhibitors of ACMSD such as pyrazinamide and diethylhexylphthalic acid ester. The production of the QA remarkably increased by adding the agents and neither atypical behavior nor a body influence such as the spasmuses were seen. To see the Trp metabolizing capacity in rats, the changes of the intermediates for the Trp - QA metabolism was examined. As a result, the rats were able to metabolize the Trp into 3-hydroxyanthranilic acid even when they were fed with the 5% Trp adding diet. The production of QA was increased up to the diet adding 2% Trp, but it was the same even in 2% and 5% Trp adding diet. It was thought that this had reached saturation by 3-HA→QA reaction by the Trp intake of 2% Trp adding diet. In conclusion, the existence of the protection mechanism that QA formed in the liver could not be taken in the encephalon was suggested. Therefore, the fracture of this protection mechanism seemed to be the root cause when the QA increased to 1000 times or more in the encephalon, and the sickness develops.