GSBS Student Publications

Title

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

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Neuroregeneration Laboratory

Date

3-1-1996

Document Type

Article

Medical Subject Headings

1-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

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: Cell Transplant. 1996 Mar-Apr;5(2):225-32.

Related Resources

Link to article in PubMed

Journal Title

Cell transplantation

PubMed ID

8689033