title: 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.
abstract: 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.
authors.affiliation: Molecular and Structural Neurobiology and Gene Therapy Program, University at Buffalo, SUNY, Buffalo, NY 14260, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Corso
authors.forename: German
authors.initials: G
authors.lastname: Torres
authors.forename: Christopher
authors.initials: C
authors.lastname: Goulah
authors.forename: Indrajit
authors.initials: I
authors.lastname: Roy
authors.forename: Angelo S
authors.initials: AS
authors.lastname: Gambino
authors.forename: John
authors.initials: J
authors.lastname: Nayda
authors.forename: Timothy
authors.initials: T
authors.lastname: Buckley
authors.forename: Ewa K
authors.initials: EK
authors.lastname: Stachowiak
authors.forename: Earl J
authors.initials: EJ
authors.lastname: Bergey
authors.forename: Haridas
authors.initials: H
authors.lastname: Pudavar
authors.forename: Purnendu
authors.initials: P
authors.lastname: Dutta
authors.forename: David C
authors.initials: DC
authors.lastname: Bloom
authors.forename: William J
authors.initials: WJ
authors.lastname: Bowers
authors.forename: Michal K
authors.initials: MK
authors.lastname: Stachowiak
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D018259:Herpesvirus 1, Human / Q000502:physiology; D008297:Male; D008845:Microinjections / Q000379:methods; D016296:Mutagenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000821:virology; D011094:Polyethyleneimine / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000172:deficiency; D051381:Rats; D011916:Rats, Inbred F344; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*; D013378:Substantia Nigra / Q000166:cytology* / Q000378:metabolism / Q000821:virology; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D011094:Polyethyleneimine; D014446:Tyrosine 3-Monooxygenase; C496350:Fgfr1 protein, rat; D011505:Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D001616:beta-Galactosidase; D004298:Dopamine