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.

Details

Serval ID
serval:BIB_71181FB92322
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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.
Journal
Journal of Neuroscience
Author(s)
Levivier M., Przedborski S., Bencsics C., Kang U.J.
ISSN
0270-6474 (Print)
ISSN-L
0270-6474
Publication state
Published
Issued date
1995
Peer-reviewed
Oui
Volume
15
Number
12
Pages
7810-7820
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Abstract
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.
Keywords
Animals, Autoradiography, Brain-Derived Neurotrophic Factor, Corpus Striatum/drug effects, Corpus Striatum/pathology, Dopamine/physiology, Fibroblasts/metabolism, Fibroblasts/transplantation, Genetic Engineering, Male, Nerve Degeneration, Nerve Growth Factors/metabolism, Nerve Tissue Proteins/metabolism, Neurons/pathology, Neurons/physiology, Oxidopamine/pharmacology, Parkinson Disease/pathology, Parkinson Disease/physiopathology, Rats, Rats, Inbred F344
Pubmed
Web of science
Create date
20/01/2008 17:35
Last modification date
20/08/2019 14:29
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