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Cell-mediated delivery of brain-derived neurotrophic factor enhances dopamine levels in an MPP+ rat model of substantia nigra degeneration

dc.contributor.authorGalpern, Wendy R.
dc.contributor.authorFrim, David M.
dc.contributor.authorTatter, Stephen B.
dc.contributor.authorAltar, C. Anthony
dc.contributor.authorBeal, M. Flint
dc.contributor.authorIsacson, Ole
dc.date2022-08-11T08:08:57.000
dc.date.accessioned2022-08-23T16:13:46Z
dc.date.available2022-08-23T16:13:46Z
dc.date.issued1996-03-01
dc.date.submitted2008-09-10
dc.identifier.citationCell Transplant. 1996 Mar-Apr;5(2):225-32.
dc.identifier.issn0963-6897 (Print)
dc.identifier.pmid8689033
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33704
dc.description.abstractBrain-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 (approximately 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8689033&dopt=Abstract">Link to article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1016/0963-6897(95)02030-6
dc.subject1-Methyl-4-phenylpyridinium; Animals; Blotting, Northern; Brain-Derived Neurotrophic Factor; Dopamine; Fibroblasts; Genetic Engineering; Male; Microinjections; Neostriatum; Nerve Degeneration; Nerve Growth Factors; Nerve Tissue Proteins; Neuroprotective Agents; RNA, Messenger; Rats; Rats, Sprague-Dawley; Substantia Nigra
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleCell-mediated delivery of brain-derived neurotrophic factor enhances dopamine levels in an MPP+ rat model of substantia nigra degeneration
dc.typeJournal Article
dc.source.journaltitleCell transplantation
dc.source.volume5
dc.source.issue2
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/368
dc.identifier.contextkey625994
html.description.abstract<p>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 (approximately 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.</p>
dc.identifier.submissionpathgsbs_sp/368
dc.contributor.departmentNeuroregeneration Laboratory
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages225-32


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