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 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.
Corso
Thomas D
TD
Molecular and Structural Neurobiology and Gene Therapy Program, University at Buffalo, SUNY, Buffalo, NY 14260, USA.
Torres
German
G
Goulah
Christopher
C
Roy
Indrajit
I
Gambino
Angelo S
AS
Nayda
John
J
Buckley
Timothy
T
Stachowiak
Ewa K
EK
Bergey
Earl J
EJ
Pudavar
Haridas
H
Dutta
Purnendu
P
Bloom
David C
DC
Bowers
William J
WJ
Stachowiak
Michal K
MK
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
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