Kwamivi Dzahini

The objectives concern the detection of chemical alterations in the brain and behavioral deficits during early phases of progressive dopaminergic lesion simulating Parkinson’s disease. This in view to ameliorate the diagnostic ability, and to propose new therapeutic processes. This is based on longitudinal approaches using experimental models with 6-OHDA and MPTP, toxic substances of the dopaminergic central neurons.
First, Parkinson’s disease etiology is approached. We investigate the relationship between striatal dopamine loss (the presumed basis of parkinsonian symptoms) and striatal dopamine metabolism. Paradoxically, we observed that dopamine release in the striatum is initialy increased in response to partial depopulation of the nigral dopamine cells as it was also observed during the early phases of Parkinson’s disease. We hypothesize that a glutamate-mediated upregulation of the striatal dopamine release delays the appearance of the symptoms, but also has deleterious consequences due to dopamine neurotoxicity.
Second, discovery of new treatments for Parkinson’s disease (PD) is impeded by an incomplete understanding of the relationship between the pathology of the disease and its symptoms. Thus we analyze the relationship between dopamine (DA) dysfunction and parkinsonism by comparing the symptoms and neurophysiologic abnormalities induced by transient blockade or permanent lesion of DA innervation in the motor striatum of behaving monkeys. We analyse the longitudinal electrophysiological follow-up of cognitive event-related potentials (feedback-related potentials) and of global oscillatory patterns that are associated to cortical dopaminergic-dependant processes and to thalamo-cortical interactions, respectively. The objective is based on chronic EEG technology in monkeys trained to cognitive tasks. The major milestone will be the characterization of neurobiological markers of early parkinson’s symptoms. We also evaluate the dynamic, interdependence of changes in striatal and cortical dopaminergic transmission during progressive mesencephalic dopaminergic lesion. The objective is based on chronic microdialysis and voltametry, and on periodic PET examinations. The major milestone will be to establish the precise timetable of fluctuations in dopaminergic transmission in target structures.