Detection of dopaminergic cell loss and neural transplantation using pharmacological MRI, PET and behavioral assessment.
We demonstrate the use of magnetic resonance imaging (MRI) for detection of neurotransmitter stimulation using the dopamine transporter ligands amphetamine and CFT (2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane) as pharmacological challenges. We demonstrate that the unilateral loss of a hemodynamic response to either amphetamine or CFT challenge by unilateral 6-hydroxydopamine lesioning is restored by transplantation of fetal dopamine neurons in the striatum. The time course for the hemodynamic changes parallels the time courses for dopamine release, measured by prior microdialysis studies, and also for the rotational behavior in the unilaterally lesioned animals. Transplantation of the fetal cells results in hemodynamic time courses after CFT or amphetamine challenges at the graft site that are identical to those induced both before transplantation and on the intact contralateral side. The transplantation also results in complete behavioral recovery. The spatial extent of the dopaminergic recovery in the lesioned striatum is the same when measured using either PET of tracer levels of [11C]CFT binding or MRI. These results show great promise for the application of pharmacological MRI for application to studies of dopamine cell loss and potential recovery in Parkinson's disease.
Chen
Y I
YI
MGH-NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown 02129, USA.
Brownell
A L
AL
Galpern
W
W
Isacson
O
O
Bogdanov
M
M
Beal
M F
MF
Livni
E
E
Rosen
B R
BR
Jenkins
B G
BG
D000661:Amphetamine; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D017690:Cell Transplantation / Q000502:physiology*; D003042:Cocaine / Q000031:analogs & derivatives; D004298:Dopamine / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors; D005260:Female; D008279:Magnetic Resonance Imaging; D017551:Microdialysis; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020955:Striatonigral Degeneration; D013563:Sympathectomy, Chemical; D014055:Tomography, Emission-Computed
D018765:Dopamine Uptake Inhibitors; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D000661:Amphetamine; D003042:Cocaine; D004298:Dopamine