Short-term GDNF treatment provides long-term rescue of lesioned nigral dopaminergic neurons in a rat model of Parkinson's disease.
Glial cell line-derived neurotrophic factor (GDNF) has been shown to exert neuroprotective effects on dopamine (DA) neurons in vivo. Here we report long-term rescue of nigral DA neurons after delayed short-term GDNF administration in a rat lesion model that reproduces the slowly progressing degenerative process seen in Parkinson's disease. GDNF injected close to the substantia nigra provided near-complete protection and persistent survival of the lesioned nigral neurons for at least 4 months after discontinuation of GDNF treatment. Long-term rescue of the nigral cells, however, was not accompanied by any significant reinnervation of the lesioned striatal target or any signs of functional recovery in either drug-induced or spontaneous motor behaviors. We conclude that not only preservation of the nigral DA neurons but also restoration of striatal DA function is necessary for functional recovery in the rat Parkinson model.
Winkler
C
C
Lund University, Wallenberg Neuroscience Center, Sweden.
Sauer
H
H
Lee
C S
CS
Björklund
A
A
D000661:Amphetamine; D000818:Animals; D000918:Antibody Specificity; D001522:Behavior, Animal / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D015259:Dopamine Agents; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009043:Motor Activity / Q000187:drug effects; D009068:Movement / Q000187:drug effects; D017072:Neostriatum / Q000166:cytology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*; D004856:Postural Balance / Q000187:drug effects; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D013378:Substantia Nigra / Q000166:cytology*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D015259:Dopamine Agents; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine