Differential effects of platelet-derived growth factor isoforms on dopamine neurons in vivo: -BB supports cell survival, -AA enhances fiber formation.
Trophic effects of platelet-derived growth factor -AA and -BB on developing (embryonic day 14) ventral mesencephalon were studied using the in vivo model of intraocular transplantation to sympathetically denervated host eyes. This model enabled studies of survival and growth of grafted brain tissue, dopaminergic fiber outgrowth from the grafts onto the host iris as well as morphological effects of platelet-derived growth factor on grafted tissue using markers for tyrosine hydroxylase and glial fibrillary acid protein. Growth of grafts was followed by repeated observations directly through the cornea of the host using a stereomicroscope. This revealed that there was no apparent effect on volume increase of mesencephalic grafts after treatments with either platelet-derived growth factor-AA (100 ng/ml buffer), platelet-derived growth factor-BB (100 ng/ml buffer) or vehicle solution (high salt buffer) alone. Growth factor treatments were administered immediately prior to grafting by incubating the grafts in the appropriate factor as well as on days 5, 10 and 15 postgrafting by administration of 5-microliters intraocular injections of similar solutions as used for incubation. Platelet-derived growth factor-AA significantly enhanced dopaminergic fiber outgrowth from mesencephalic grafts when compared to both platelet-derived growth factor-BB and controls, without an accompanying rise in the number of tyrosine hydroxylase-positive neurons. In contrast, a significantly greater number of tyrosine hydroxylase-positive neurons was seen in grafts treated with platelet-derived growth factor-BB but without an accompanying increase in outgrowth of dopamine-containing fibers.(ABSTRACT TRUNCATED AT 250 WORDS)
Giacobini
M M
MM
Department of Histology & Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Almström
S
S
Funa
K
K
Olson
L
L
D000818:Animals; D000077214:Becaplermin; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D016332:Fetal Tissue Transplantation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects; D006651:Histocytochemistry; D007150:Immunohistochemistry; D007498:Iris / Q000502:physiology; D008297:Male; D008636:Mesencephalon / Q000196:embryology; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; C075278:platelet-derived growth factor A; D000077214:Becaplermin; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine