Monitoring and Counteracting Functional Deterioration in Parkinson's Disease: A Multilevel Integrative Approach in a Primate Model System

摘要

It is still largely unknown what the general course is in the progression of Parkinson's disease (PD). Presumably more than one factor is responsible. There is evidence suggesting that metabolic compromise, excitotoxicity and oxidative stress are involved in the neurodegenerative process causing PD. To investigate the connection of excitotoxicity and oxidative stress with metabolic compromise in the development of the disease, anti-excitotoxic treatment with riluzole and anti-oxidant treatment with EGCG will be compared to untreated controls and to a standard treatment with L-DOPA in a MPTP induced Parkinson model. We hypothesize that critical changes indicating the nature of the gradual patho-physiological changes leading to PD will be revealed if anti-oxidants or anti-excitatory treatments are given in a situation where the brain is susceptible to develop PD. The comparison, of the results on the different levels of research, between the neuroprotective regimes and the symptom control drug L-DOPA will give insight in the relative role of the different markers for neuroprotection and behavioral output. In particular relatively new technologies such as differential proteomics and sleep research will yield novel insights. In this report period new test methods were developed, the use of brain imaging or neurophysiology was validated and the dose range finding of the test compounds was performed. The highest sign-free dose will be used in the neuroprotective experiments.