METHODS FOR KYNURENINE SYSTEM IN HUNTINGTON'S DISEASE

227-43个元件初始多参数数据库的分析

The analysis of an initial multiparameter data base of 227-43 components in 144 brain samples indicated significant differences in the kynurenic, serotonergic and dopaminergic systems between Huntington's Disease (HD) and control putamen. These were consistent with the quinolinic acid hypothesis of neuronal degeneration. In the Phase II study, we purpose to create a larger data base of approximately 4000 samples from additional tissues and among different disorders using the methods for multiparameter measurements and the procedures for rapid data reduction, transfer and management developed for the ESA Neurochemical Analyzer (NCA). Tissues will be analyzed from several different HD and control brain regions to examine whether the kynurenic abnormalities are primary or secondary to gliosis, and in plasma and CSF to determine if they are general expressions of a defect. Similar tissues will be examined among other disorders (Alzheimer;s and Parkinson"s disease, ALS, Schizophrenia) to determine if the abnormalities are unique to HD and to rule out drug related anomalies. Measurements to test the HD model will be made on animal models of acute and chronic excitotoxin lesions and in feeding models with and without portacaval shunts. The long term goal of the work is to provide a data base and biochemical model of HD that can be used as a guide to develop therapeutic strategies.