Transfection of tyrosine kinase deleted FGF receptor-1 into rat brain substantia nigra reduces the number of tyrosine hydroxylase expressing neurons and decreases concentration levels of striatal dopamine

The effects of HSV-1 amplicon and polyethyleneimine (PEI)-mediated transfection of dominant negative FGF receptor-1 mutant FGFR1(TK−) into the rat brain substantia nigra (SN) were examined in vivo to model the reduced FGF signaling documented to occur in Parkinson's disease. The number of SN ne...

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Bibliographic Details
Published in:Brain research. Molecular brain research. 2005-10, Vol.139 (2), p.361-366
Main Authors: Corso, Thomas D., Torres, German, Goulah, Christopher, Roy, Indrajit, Gambino, Angelo S., Nayda, John, Buckley, Timothy, Stachowiak, Ewa K., Bergey, Earl J., Pudavar, Haridas, Dutta, Purnendu, Bloom, David C., Bowers, William J., Stachowiak, Michal K.
Format: Article
Language:English
Subjects:
Animals
beta-Galactosidase - metabolism
Biological and medical sciences
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Dopamine - metabolism
Fibroblast growth factor receptor
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation - drug effects
Gene Expression Regulation - physiology
Gene transfection
Herpes simplex virus 1
Herpesvirus 1, Human - physiology
Male
Medical sciences
Microinjections - methods
Mutagenesis - physiology
Neurology
Neurons - metabolism
Neurons - virology
Parkinson's disease
Polyethyleneimine
Polyethyleneimine - pharmacology
Protein-Tyrosine Kinases - deficiency
Rats
Rats, Inbred F344
Receptor, Fibroblast Growth Factor, Type 1 - genetics
Receptor, Fibroblast Growth Factor, Type 1 - metabolism
Substantia nigra
Substantia Nigra - cytology
Substantia Nigra - metabolism
Substantia Nigra - virology
Time Factors
Transfection - methods
Tyrosine 3-Monooxygenase - metabolism
Vertebrates: nervous system and sense organs
β-galactosidase
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Summary:The effects of HSV-1 amplicon and polyethyleneimine (PEI)-mediated transfection of dominant negative FGF receptor-1 mutant FGFR1(TK−) into the rat brain substantia nigra (SN) were examined in vivo to model the reduced FGF signaling documented to occur in Parkinson's disease. The number of SN neurons that expressed tyrosine hydroxylase (TH) was significantly reduced following HSV-1 FGFR1(TK−) intranigral delivery and similar changes were observed after PEI-mediated FGFR1(TK−) transfections. Further, we also observed a significantly lower striatal dopamine content following the PEI transfection of FGFR1(TK−). Thus, we conclude that reduced FGF signaling in the SN of Parkinsonian patients could play a role in the impaired dopaminergic transmission associated with the degenerative disease.
ISSN:0169-328X
1872-6941
DOI:10.1016/j.molbrainres.2005.05.032