Glial cell line-derived neurotrophic factor reverses motor impairment in 16-17 month old rats.
Aging is accompanied with declines in motoric function which may be the result of deficits in central nervous system dopaminergic function. Glial cell line-derived neurotrophic factor (GDNF) has been shown to have neuroprotective and restorative effects on dopaminergic neurons of the nigrostriatal pathway in young rats. In this study, 10, 40, or 60 micrograms GDNF or vehicle was injected intrastriatally in 16-17 month old Fischer 344 rats. Coordination and muscle strength as determined by performance on an inclined balance beam and a wire grip strength test were monitored for up to 5 weeks post-injection. GDNF elicited dose-dependent improvements in motor coordination without concurrent increases in strength. The highest dose tested produced > 79% improvement in motor coordination, resulting in performance scores approaching those achieved by 3 month old rats tested concurrently. These findings indicate GDNF produces profound improvement in the motoric function of mature rats, which may be related to dopaminergic circuits.
Bowenkamp
K E
KE
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
Lapchak
P A
PA
Hoffer
B J
BJ
Bickford
P C
PC
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D004298:Dopamine / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005684:Gait / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018737:Hand Strength / Q000502:physiology; D007267:Injections; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000502:physiology; D009414:Nerve Growth Factors; D009416:Nerve Regeneration / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D015854:Up-Regulation / Q000187:drug effects
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D004298:Dopamine