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

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 16580106
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Food science
• Research Institution: The University of Shiga Prefecture
• Principal Investigator: SHIBATA Katsumi The University of Shiga Prefecture, Department of Life Style Studies, Professor, 人間文化学部, 教授 (40131479)
• Project Period (FY): 2004 – 2005
• Keywords: neurotoxin / quinolinic acid / tryptophan / kynurenic acid

Research Abstract

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.