COMBINED PET MRS BRAIN STUDIES SHOW DYNAMIC AND LONG-TERM PHYSIOLOGICAL-CHANGES IN A PRIMATE MODEL OF PARKINSON-DISEASE/

We used brain imaging to study long-term neurodegenerative and bioadap tive neurochemical changes in a primate model of Parkinson disease. We gradually induced a selective loss of nigrostriatal dopamine neurons, similar to that of Parkinson disease, by creating oxidative stress th rough infusion of the mitochondrial complex 1 inhibitor MPTP for 14 +/ - 5 months. Repeated evaluations over 3 years by positron emission tom ography (PET) demonstrated progressive and persistent loss of neuronal dopamine pre-synaptic re-uptake sites; repeated magnetic resonance sp ectroscopy (MRS) studies indicated a 23-fold increase in lactate and m acromolecules in the striatum region of the brain for up to 10 months after the last administration of MPTP. By 2 years after the MPTP infus ions, these MRS striatal lactate and macromolecule values had returned to normal levels. In contrast, there were persistent increases in str iatal choline and decreases in N-acetylaspartate. Thus, these combined PET/MRS studies demonstrate patterns of neurochemical changes that ar e both dynamic and persistent long after selective dopaminergic degene ration.