Cell-Mediated Delivery of Brain-Derived Neurotrophic Factor Enhances Dopamine Levels in an Mpp+ Rat Model of Substantia Nigra Degeneration
Brain-derived neurotrophic factor (BDNF) promotes the survival of fetal mesencephalic dopaminergic cells and protects dopaminergic neurons against the toxicity of MPP+ in vitro. Supranigral implantation of fibroblasts genetically engineered to secrete BDNF attenuates the loss of substantia nigra par...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
1996-03-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/096368979600500211 |
| _version_ | 1818259093492596736 |
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| author | Wendy R. Galpern David M. Frim Stephen B. Tatter C. Anthony Altar M. Flint Beal Ole Isacson |
| author_facet | Wendy R. Galpern David M. Frim Stephen B. Tatter C. Anthony Altar M. Flint Beal Ole Isacson |
| author_sort | Wendy R. Galpern |
| collection | DOAJ |
| description | Brain-derived neurotrophic factor (BDNF) promotes the survival of fetal mesencephalic dopaminergic cells and protects dopaminergic neurons against the toxicity of MPP+ in vitro. Supranigral implantation of fibroblasts genetically engineered to secrete BDNF attenuates the loss of substantia nigra pars compacta (SNc) dopaminergic neurons associated with striatal infusion of MPP+ in the adult rat. Using this MPP+ rat model of nigral degeneration, we evaluated the neurochemical effects of supranigral, cell-mediated delivery of BDNF on substantia nigra (SN) dopamine (DA) content and turnover. Genetically engineered BDNF-secreting fibroblasts (~12 ng BDNF/24 h) were implanted dorsal to the SN 7 days prior to striatal MPP+ administration. The present results demonstrate that BDNF-secreting fibroblasts, as compared to control fibroblasts, enhance SN DA levels ipsilateral as well as contralateral to the graft without altering DA turnover. This augmentation of DA levels suggests that local neurotrophic factor delivery by genetically engineered cells may provide a therapeutic strategy for preventing neuronal death or enhancing neuronal function in neurodegenerative diseases characterized by dopaminergic neuronal dysfunction, such as Parkinson's disease. |
| first_indexed | 2024-12-12T18:09:58Z |
| format | Article |
| id | doaj.art-62b0225114b840b587aade66e16f8464 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-12T18:09:58Z |
| publishDate | 1996-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-62b0225114b840b587aade66e16f84642022-12-22T00:16:24ZengSAGE PublishingCell Transplantation0963-68971555-38921996-03-01510.1177/096368979600500211Cell-Mediated Delivery of Brain-Derived Neurotrophic Factor Enhances Dopamine Levels in an Mpp+ Rat Model of Substantia Nigra DegenerationWendy R. Galpern0David M. Frim1Stephen B. Tatter2C. Anthony Altar3M. Flint Beal4Ole Isacson5University of Massachusetts Medical Center, Worcester, MA 01655 USANeurology and Neurosurgery Service, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA 02115 USANeurology and Neurosurgery Service, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA 02115 USARegeneron Pharmaceuticals, Inc., Tarrytown, NY 10591 USANeurology and Neurosurgery Service, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA 02115 USANeurology and Neurosurgery Service, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA 02115 USABrain-derived neurotrophic factor (BDNF) promotes the survival of fetal mesencephalic dopaminergic cells and protects dopaminergic neurons against the toxicity of MPP+ in vitro. Supranigral implantation of fibroblasts genetically engineered to secrete BDNF attenuates the loss of substantia nigra pars compacta (SNc) dopaminergic neurons associated with striatal infusion of MPP+ in the adult rat. Using this MPP+ rat model of nigral degeneration, we evaluated the neurochemical effects of supranigral, cell-mediated delivery of BDNF on substantia nigra (SN) dopamine (DA) content and turnover. Genetically engineered BDNF-secreting fibroblasts (~12 ng BDNF/24 h) were implanted dorsal to the SN 7 days prior to striatal MPP+ administration. The present results demonstrate that BDNF-secreting fibroblasts, as compared to control fibroblasts, enhance SN DA levels ipsilateral as well as contralateral to the graft without altering DA turnover. This augmentation of DA levels suggests that local neurotrophic factor delivery by genetically engineered cells may provide a therapeutic strategy for preventing neuronal death or enhancing neuronal function in neurodegenerative diseases characterized by dopaminergic neuronal dysfunction, such as Parkinson's disease.https://doi.org/10.1177/096368979600500211 |
| spellingShingle | Wendy R. Galpern David M. Frim Stephen B. Tatter C. Anthony Altar M. Flint Beal Ole Isacson Cell-Mediated Delivery of Brain-Derived Neurotrophic Factor Enhances Dopamine Levels in an Mpp+ Rat Model of Substantia Nigra Degeneration Cell Transplantation |
| title | Cell-Mediated Delivery of Brain-Derived Neurotrophic Factor Enhances Dopamine Levels in an Mpp+ Rat Model of Substantia Nigra Degeneration |
| title_full | Cell-Mediated Delivery of Brain-Derived Neurotrophic Factor Enhances Dopamine Levels in an Mpp+ Rat Model of Substantia Nigra Degeneration |
| title_fullStr | Cell-Mediated Delivery of Brain-Derived Neurotrophic Factor Enhances Dopamine Levels in an Mpp+ Rat Model of Substantia Nigra Degeneration |
| title_full_unstemmed | Cell-Mediated Delivery of Brain-Derived Neurotrophic Factor Enhances Dopamine Levels in an Mpp+ Rat Model of Substantia Nigra Degeneration |
| title_short | Cell-Mediated Delivery of Brain-Derived Neurotrophic Factor Enhances Dopamine Levels in an Mpp+ Rat Model of Substantia Nigra Degeneration |
| title_sort | cell mediated delivery of brain derived neurotrophic factor enhances dopamine levels in an mpp rat model of substantia nigra degeneration |
| url | https://doi.org/10.1177/096368979600500211 |
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