Short-Term GDNF Treatment Provides Long-Term Rescue of Lesioned Nigral Dopaminergic Neurons in a Rat Model of Parkinson’s Disease
Open accessAbstract
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.
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Growth factor-mediated prevention of neuronal loss in transection models has predicted protection from disease-specific mechanisms in other models.
“Indeed, growth factor–mediated prevention of neuronal loss in transection models has predicted protection from disease-specific mechanisms in other models22–25.”
From Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease (2009) · cites this paper as [23]
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- Authors
- Winkler, C., Sauer, H., Lee, C. S., & Björklund, A.
- Affiliations
- Lund University (SE)
- Genentech (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1996-11-15
- Volume
- 16
- Issue
- 22
- Pages
- 7206-7215
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6578933
- OpenAlex
- W1795898662
- Cited by
- 258
- References
- 27
- Citations by year
- 2025: 6 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 5 · 2017: 3 · 2016: 6 · 2015: 9 · 2014: 4 · 2013: 9 · 2012: 8
- FWCI
- 13.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Science Foundation
- Genentech
- Medical Research Council
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- glial cell line-derived neurotrophic factor, Parkinson's disease, substantia nigra, dopaminergic neurons, neuroprotection, neuronal survival, striatal reinnervation, functional recovery, motor behavior, rat model
- MeSH terms
- Amphetamine, Animals, Antibody Specificity, Behavior, Animal, Disease Models, Animal, Dopamine, Postural Balance, Female, Motor Activity, Movement, Nerve Growth Factors, Nerve Regeneration, Nerve Tissue Proteins, Neurons, Parkinson Disease, Secondary, Rotation, Substantia Nigra, Time Factors, Tyrosine 3-Monooxygenase, Dopamine Agents, Oxidopamine, Cell Death, Neostriatum, Rats, Sprague-Dawley, Presynaptic Terminals, Neuroprotective Agents, Glial Cell Line-Derived Neurotrophic Factor, Rats
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