Fibroblast growth factors enhance dopamine fiber formation from nigral grafts.
Members of the fibroblast growth factor (FGF) family have earlier been shown to exert potent trophic effects on cells of both the central and peripheral nervous system. The presence of FGF-1 and -2 (FGF-1, acidic FGF; FGF-2, basic FGF) has recently been demonstrated in the dopaminergic cells of substantia nigra in rat and FGF-2 has been shown to be able to increase survival and promote neurite outgrowth of cultured mesencephalic neurons. In the presence study, we have investigated possible trophic effects of FGF-1 and FGF-2 on developing rat ventral mesencephalon of different fetal stages by utilizing the in vivo method of intraocular transplantation to sympathetically denervated hosts. Survival and growth of developing grafts after growth factor treatment was followed in oculo. The Falck-Hillarp technique was used for evaluation of catecholaminergic fiber outgrowth into the host iris in whole-mount preparations. FGF-2 significantly increased the volume of the mesencephalic grafts when compared to grafts treated with the vehicle alone. The mean volume of FGF-1-treated grafts was larger than that of control grafts, but this difference was not statistically significant. FGF-1 significantly increased the area of outgrowth of dopaminergic fibers into the host iris without a corresponding increase in the number of dopaminergic neurons, as evaluated by TH immunohistochemistry. FGF-2 had no effect on dopaminergic fiber outgrowth on grafted E14 ventral mesencephalon but it did have a significant effect on fiber outgrowth from E15 and E16 grafts. Moreover, the FGF-2 treated E16 grafts contained a larger number of dopaminergic neurons as compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Giacobini
M M
MM
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Strömberg
I
I
Almström
S
S
Cao
Y
Y
Olson
L
L
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D016380:Brain Tissue Transplantation / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D016332:Fetal Tissue Transplantation / Q000502:physiology; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000637:transplantation; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D015415:Biomarkers; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine