Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo
Abstract
Glial-cell-line-derived neurotrophic factor (GDNF), a recently cloned new member of the transforming growth factor-beta superfamily, promotes survival of cultured fetal mesencephalic dopamine neurons and is expressed in the developing striatum. There have, however, been no reports about effects of GDNF in situ. We have used the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces parkinsonian symptoms in man, to determine whether GDNF might exert protective or regenerative effects in vivo in the adult nigrostriatal dopamine system in C57/B1 mice. GDNF injected over the substantia nigra or in striatum before MPTP potently protects the dopamine system, as shown by numbers of mesencephalic dopamine nerve cell bodies, dopamine nerve terminal densities and dopamine levels. When GDNF is given after MPTP, dopamine levels and fibre densities are significantly restored. In both cases, motor behaviour is increased above normal levels. We conclude that intracerebral GDNF administration exerts both protective and reparative effects on the nigrostriatal dopamine system, which may have implications for the development of new treatment strategies for Parkinson's disease.
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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 [22]
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- Authors
- Tomac, A., Lindqvist, E., Lin, L.-F. H., Ögren, S. O., Young, D., Hoffer, B. J., & Olson, L.
- Affiliations
- Karolinska Institutet (SE)
- State of Colorado (US)
- University of Colorado Denver (US)
- Venue
- Nature
- Published
- 1995-01-26
- Volume
- 373
- Issue
- 6512
- Pages
- 335-339
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2063893203
- Cited by
- 1,079
- References
- 20
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 9 · 2023: 6 · 2022: 15 · 2021: 15 · 2020: 14 · 2019: 15 · 2018: 17 · 2017: 17 · 2016: 17 · 2015: 23 · 2014: 29 · 2013: 28 · 2012: 24
- FWCI
- 68.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- 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, nigrostriatal pathway, MPTP-induced neurotoxicity, Parkinson's disease, neuroprotection, substantia nigra, striatum, dopamine levels, motor behavior, neurotrophic factors
- MeSH terms
- Animals, Dopamine, Humans, Male, Mice, Inbred C57BL, Motor Neurons, Nerve Degeneration, Nerve Growth Factors, Nerve Tissue Proteins, Parkinson Disease, Secondary, Substantia Nigra, Tyrosine 3-Monooxygenase, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Glial Cell Line-Derived Neurotrophic Factor, Mice
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