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PMID: 8929429 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Short-term GDNF treatment provides long-term rescue of lesioned nigral dopaminergic neurons in a rat model of Parkinson's disease.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 16 ·No. 22 ·1996-11-15 ·Pages 7206-15

Winkler C, Sauer H, Lee CS, Björklund A

Abstract

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.

MeSH Terms
Amphetamine Animals Antibody Specificity Behavior, Animal/drug effects Cell Death/drug effects Disease Models, Animal Dopamine/physiology Dopamine Agents Female Glial Cell Line-Derived Neurotrophic Factor Motor Activity/drug effects Movement/drug effects Neostriatum/cytology Nerve Growth Factors/pharmacology Nerve Regeneration/drug effects Nerve Tissue Proteins/pharmacology Neurons/cytology,drug effects,enzymology Neuroprotective Agents/pharmacology Oxidopamine Parkinson Disease, Secondary/chemically induced,drug therapy Postural Balance/drug effects Presynaptic Terminals/drug effects Rats Rats, Sprague-Dawley Rotation Substantia Nigra/cytology Time Factors Tyrosine 3-Monooxygenase/analysis
Chemicals
Dopamine Agents Gdnf protein, rat Glial Cell Line-Derived Neurotrophic Factor Nerve Growth Factors Nerve Tissue Proteins Neuroprotective Agents Oxidopamine Amphetamine Tyrosine 3-Monooxygenase Dopamine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Winkler C
Lund University, Wallenberg Neuroscience Center, Sweden.
Sauer H
Lee C S
Björklund A
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1996-11-15
Pages
7206-15
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6578933
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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