Mapping of brain function after MPTP-induced neurotoxicity in a primate Parkinson's disease model.
Neurophysiological studies of the brain in normal and Parkinson's disease (PD) patients have indicated intricate connections for basal ganglia-induced control of signaling into the motor cortex. To investigate if similar mechanisms are controlling function in the primate brain (Macaca fascicularis) after MPTP-induced neurotoxicity, we conducted PET studies of cerebral blood flow, oxygen and glucose metabolism, dopamine transporter, and D2 receptor function. Our observations after MPTP-induced dopamine terminal degeneration of the caudate and putamen revealed increased blood flow (15%) in the globus pallidus (GP), while blood flow was moderately decreased (15-25%) in the caudate, putamen, and thalamus and 40 % in the primary motor cortex (PMC). Oxygen extraction fraction was moderately increased (10-20%) in other brain areas but the thalamus, where no change was observable. Oxygen metabolism was increased in the GP and SMA (supplementary motor area including premotor cortex, Fig. 3) by a range of 20-40% and decreased in the putamen and caudate and in the PMC. Glucose metabolism was decreased in the caudate, putamen, thalamus, and PMC (range 35-50%) and enhanced in the GP by 15%. No change was observed in the SMA. In the parkinsonian primate, [(11)C]CFT (2beta-carbomethoxy-3beta-(4-fluorophenyltropane) dopamine transporter binding was significantly decreased in the putamen and caudate (range 60-65%). [(11)C]Raclopride binding of dopamine D(2) receptors did not show any significant changes. These experimental results obtained in primate studies of striato-thalamo-cortico circuitry show a similar trend as hypothetized in Parkinson's disease-type degeneration.
Brownell
Anna Liisa
AL
Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA. abrownell@partners.org
Canales
Kelly
K
Chen
Y Iris
YI
Jenkins
Bruce G
BG
Owen
Christopher
C
Livni
Elijahu
E
Yu
Meixiang
M
Cicchetti
Francesca
F
Sanchez-Pernaute
Rosario
R
Isacson
Ole
O
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D001923:Brain Chemistry / Q000502:physiology; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000502:physiology; D015259:Dopamine Agents / Q000633:toxicity*; D050483:Dopamine Plasma Membrane Transport Proteins; D004734:Energy Metabolism / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D009419:Nerve Tissue Proteins; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000502:physiology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D015203:Reproducibility of Results; D014055:Tomography, Emission-Computed
D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D005947:Glucose; D010100:Oxygen