Nature Medicine
4, 1308 - 1312 (1998)
doi:10.1038/3300
Combined PET/MRS brain studies show dynamic and long-term physiological
changes in a primate model of Parkinson diseaseAnna-Liisa Brownell1, 3, Bruce G. Jenkins1, David R. Elmaleh1, Terrence W. Deacon3, Roger D. Spealman4
& Ole Isacson2, 31
Department of Radiology, Massachusetts General Hospital,
and Program in Neuroscience Harvard Medical School, Boston,
Massachusetts 02114, USA
2
Department of Neurology, Massachusetts General Hospital,
and Program in Neuroscience Harvard Medical School, Boston,
Massachusetts 02114, USA
3
Neuroregeneration Laboratories, McLean Hospital,
Belmont, Massachusetts 02178, USA
4
New England Regional Primate Research Center,
Southborough, Massachusetts 01772, USA
Correspondence should be addressed to Ole Isacson 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.
|
