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 bioadaptive 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 through infusion of the mitochondrial complex 1 inhibitor MPTP for 14+/-5 months. Repeated evaluations over 3 years by positron emission tomography (PET) demonstrated progressive and persistent loss of neuronal dopamine pre-synaptic re-uptake sites; repeated magnetic resonance spectroscopy (MRS) studies indicated a 23-fold increase in lactate and macromolecules in the striatum region of the brain for up to 10 months after the last administration of MPTP. By 2 years after the MPTP infusions, these MRS striatal lactate and macromolecule values had returned to normal levels. In contrast, there were persistent increases in striatal choline and decreases in N-acetylaspartate. Thus, these combined PET/MRS studies demonstrate patterns of neurochemical changes that are both dynamic and persistent long after selective dopaminergic degeneration.
Brownell
A L
AL
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Jenkins
B G
BG
Elmaleh
D R
DR
Deacon
T W
TW
Spealman
R D
RD
Isacson
O
O
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008252:Macaca fascicularis; D009682:Magnetic Resonance Spectroscopy; D009410:Nerve Degeneration / Q000473:pathology; D009474:Neurons / Q000473:pathology / Q000502:physiology; D010302:Parkinson Disease, Secondary / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D007773:Lactates; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine