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Intrastriatal implantation of fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevents degeneration of dopaminergic neurons in a rat model of Parkinson’s disease
Open accessAbstract
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of the dopaminergic neurons of the substantia nigra pars compacta (SNpc). Although various treatments are successfully used to alleviate the symptoms of PD, none of them prevents or halts the neurodegenerative process of the disease. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of proteins, supports the survival and the differentiation of dopaminergic neurons. BDNF also prevents the death of dopaminergic neurons in vitro, which suggests that it may be of possible use in the development of neuroprotective therapies for PD. To determine whether BDNF is neuroprotective for SNpc dopaminergic neurons in the adult brain, we used a rat model of PD in which degeneration of 60-70% of these neurons was induced by an intrastriatal injection of 6-hydroxydopamine (6-OHDA). We report here that intrastriatal grafts of fibroblasts genetically engineered to produce BDNF partially prevent the loss of nerve terminals and completely prevent the loss of cell bodies of the nigrostriatal dopaminergic pathway that is induced by the intrastriatal injection of 6-OHDA. In contrast, the implantation of control fibroblasts that did not produce BDNF failed to protect nerve terminals and cell bodies against 6-OHDA-induced damage. Our observation that grafts of BDNF-producing fibroblasts protect against 6-OHDA-induced degeneration of SNpc dopaminergic neurons in the adult rat brain opens new perspectives for treatments aimed at the prevention of neurodegeneration in PD, using gene therapy and neurotrophic factors such as BDNF.
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“In the vast majority of studies with BDNF administration before induction of parkinsonism, the research results revealed at least partial prevention of neuronal cell loss [89,90,92,93,99,101].”
From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [101]
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Metadata
- Authors
- Levivier, M., Przedborski, S., Bencsics, C., & Kang, U.
- Affiliations
- Columbia University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1995-12-01
- Volume
- 15
- Issue
- 12
- Pages
- 7810-7820
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6577965
- OpenAlex
- W1590012920
- Cited by
- 274
- References
- 25
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 6 · 2020: 11 · 2019: 5 · 2018: 9 · 2017: 3 · 2016: 9 · 2015: 11 · 2014: 11 · 2013: 8 · 2012: 9
- FWCI
- 7.32
- 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)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Irving A. Hansen Memorial Foundation
- National Institutes of Health (5r29ns032080-05, 5k08ns001724-03)
- Parkinsonfonden
- Fogarty International Center
- National Institute of Neurological Disorders and Stroke (1-K08-NS01724-01, R29 NS32080)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, brain-derived neurotrophic factor, dopaminergic neuron loss, substantia nigra pars compacta, 6-hydroxydopamine, gene therapy, neuroprotection, nigrostriatal pathway, neurotrophic factors
- MeSH terms
- Animals, Autoradiography, Corpus Striatum, Dopamine, Fibroblasts, Genetic Engineering, Male, Nerve Degeneration, Nerve Growth Factors, Nerve Tissue Proteins, Neurons, Parkinson Disease, Rats, Inbred F344, Oxidopamine, Brain-Derived Neurotrophic Factor, Rats
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