Neuroscience 2004 Abstract
| Presentation Number: | 790.6 |
|---|---|
| Abstract Title: | Functional MRI studies of nigrostriatal effects of GDNF in alert parkinsonian monkeys. |
| Authors: |
Zhang, Z.*1,2,3
; Andersen, A.1,2,3
; Grondin, R.1,2,3
; Forman, E.1
; Dunlap, M.1
; Hardy, P.3
; Gerhardt, G.1,2,3
; Gash, D.1,2,3
1Anat. and Neurobiology, Univ. of Kentucky Col. of Med., Lexington, KY 2M.K. Udall PD Ctr. of Excellence, Univ. of Kentucky Col. of Med., Lexington, KY 3Magnetic Resonance Imaging and Spectroscopy Ctr., Univ. of Kentucky Col. of Med., Lexington, KY |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Neurodegenerative Disorders -- Parkinson's Disease: Experimental therapies |
| Session: |
790. Parkinson's Disease: Gene Therapy, Growth Factors, and Grafts (Animal Models) I Poster |
| Presentation Time: | Tuesday, October 26, 2004 2:00 PM-3:00 PM |
| Location: | San Diego Convention Center - Hall A-H, Board # UU13 |
| Keywords: | fMRI, GDNF, PARKINSON, MONKEY |
Our previous studies have demonstrated that functional magnetic resonance imaging (fMRI) can be used to non-invasively map dopaminergic drug-evoked activation in awake parkinsonian monkeys. In the present study, blood oxygen level dependent (BOLD) changes in the nigrostriatal pathway in response to apomorphine (mixed D1/D2 receptor agonist) administration were mapped by fMRI in three unilateral MPTP-treated, behaviorally characterized rhesus monkeys. Then, the animals were implanted in the lesioned putamen with a multi-port catheter attached to a pump placed in a jacket worn by the animals. Continuous unilateral infusion of 22.5 µg/day GDNF was initiated, with behavioral and fMRI studies being resumed six weeks later. All animals showed improvement in PD features assessed by a parkinsonian rating scale and movement speed evaluated by an automated video tracking system. Prior to GDNF treatment, the substantia nigra and the putamen on the MPTP lesioned side were strongly activated by apomorphine, while the opposite response was seen in the contralateral substantia nigra and putamen. Pronounced BOLD changes in the substantia nigra and putamen on both sides of the brain were attenuated after 6 weeks of intraputamenal GDNF infusion, and continued to diminish after 12 weeks of therapy. The results suggest that GDNF treatment normalizes dopamine receptor responses in the nigrostriatal pathway to dopaminergic drugs. Further data analysis is in progress. The preliminary results indicate that fMRI can be used to non-invasively monitor GDNF-induced changes in the nigrostriatal system in alert hemiparkinsonian monkeys.
Supported by USPHS NIH grants AG13494, NS39787 and MH01245.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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