Effects of chronic intraputamenal infusion of glial cell line-derived neurotrophic factor (GDNF) in aged Rhesus monkeys.
In this study, 17-23 year old Rhesus monkeys were used as an early model of Parkinson's disease (PD). Four animals received chronic infusions of GDNF and four received vehicle infusions into the right putamen via programmable pumps for 8 weeks. Weekly videotaping was performed to record general motor performance and a monkey movement analysis panel (mMAP) was used to quantify fine and coarse upper limb motor performance. The GDNF-treated animals showed significant improvements in their overall motor performance in the last 3 weeks of the study compared to controls. Fine motor time of the upper limbs improved significantly in both the GDNF-treated and control animals. After 8 weeks of drug administration, the animals were euthanized and tissue punches were taken from the basal ganglia for measures of dopamine (DA) and DA metabolite levels. In the right putamen, GDNF infusion produced a 217% increase in homovanillic acid (HVA) levels. In addition, DA levels increased by 50% in the right caudate nucleus and there were 122 and 76% increases in 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the right and left caudate nucleus, respectively. HVA levels were also seen to be increased by 212% in the right caudate nucleus. Finally, changes were seen in the right globus pallidus, with 390 and 171% increases in DA and HVA levels, respectively. These data support the hypothesis that GDNF may be beneficial for the treatment of damaged or degenerating DA neurons in aged monkeys and possibly in aged humans.
Maswood
Navin
N
Department of Anatomy and Neurobiology, College of Medicine, University of Kentucky, 306 Davis Mills Building, Lexington, KY 40536-0098, USA.
Grondin
Richard
R
Zhang
Zhiming
Z
Stanford
John A
JA
Surgener
Stewart P
SP
Gash
Don M
DM
Gerhardt
Greg A
GA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D001132:Arm; D004298:Dopamine / Q000378:metabolism; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006719:Homovanillic Acid / Q000378:metabolism; D015918:Infusion Pumps, Implantable; D008253:Macaca mulatta; D009043:Motor Activity / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000378:metabolism; D011699:Putamen / Q000187:drug effects* / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism
D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid