Title

Detection of dopaminergic cell loss and neural transplantation using pharmacological MRI, PET and behavioral assessment

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences

Date

11-5-1999

Document Type

Article

Medical Subject Headings

Amphetamine; Animals; Behavior, Animal; Cell Transplantation; Cocaine; Dopamine; Dopamine Uptake Inhibitors; Female; Magnetic Resonance Imaging; Microdialysis; Neurons; Rats; Rats, Sprague-Dawley; Striatonigral Degeneration; Sympathectomy, Chemical; Tomography, Emission-Computed

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: Neuroreport. 1999 Sep 29;10(14):2881-6.

Related Resources

Link to article in PubMed