TY - JOUR
T1 - Mapping of brain function after MPTP-induced neurotoxicity in a primate Parkinson's disease model
AU - Brownell, Anna Liisa
AU - Canales, Kelly
AU - Chen, Y. Iris
AU - Jenkins, Bruce G.
AU - Owen, Christopher
AU - Livni, Elijahu
AU - Yu, Meixiang Max
AU - Cicchetti, Francesca
AU - Sanchez-Pernaute, Rosario
AU - Isacson, Ole
PY - 2003/10/1
Y1 - 2003/10/1
N2 - 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, [11C]CFT (2β -carbomethoxy-3β-(4-fluorophenyltropane) dopamine transporter binding was significantly decreased in the putamen and caudate (range 60-65%). [ 11C]Raclopride binding of dopamine D2 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.
AB - 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, [11C]CFT (2β -carbomethoxy-3β-(4-fluorophenyltropane) dopamine transporter binding was significantly decreased in the putamen and caudate (range 60-65%). [ 11C]Raclopride binding of dopamine D2 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.
KW - MPTP
KW - Parkinson's disease
KW - Positron emission tomography
KW - Volume rendering
UR - http://www.scopus.com/inward/record.url?scp=0142074677&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0142074677&partnerID=8YFLogxK
U2 - 10.1016/S1053-8119(03)00348-3
DO - 10.1016/S1053-8119(03)00348-3
M3 - Article
C2 - 14568476
AN - SCOPUS:0142074677
VL - 20
SP - 1064
EP - 1075
JO - NeuroImage
JF - NeuroImage
SN - 1053-8119
IS - 2
ER -