Enhanced axonal growth from fetal human bcl-2 transgenic mouse dopamine neurons transplanted to the adult rat striatum.
Embryonic neurons transplanted to the adult CNS extend axons only for a developmentally defined period. There are certain intercellular factors that control the axonal extension, one of which may be the expression of the bcl-2 protein. In this study, rats with complete striatal dopamine fiber denervation received embryonic day 14 mouse ventral mesencephalon cells overexpressing human bcl-2 or control wild-type ventral mesencephalon cells. All rats were treated with cyclosporine to prevent rejection and the surviving grafts were analyzed for cell survival and outgrowth of dopaminergic fibers. The results demonstrate that bcl-2 overexpression does not enhance neuronal graft survival. However, the bcl-2 overexpressing neurons had a higher number of dopaminergic fibers that grew longer distances. These results show that overexpression of bcl-2 can result in longer distance axonal growth of transplanted fetal dopaminergic neurons and that genetic modification of embryonic donor cells may enhance their ability to reinnervate a neuronal target territory.
Holm
K H
KH
Neuroregeneration Laboratory, McLean Hospital and Program in Neuroscience, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
Cicchetti
F
F
Bjorklund
L
L
Boonman
Z
Z
Tandon
P
P
Costantini
L C
LC
Deacon
T W
TW
Huang
X
X
Chen
D F
DF
Isacson
O
O
D000818:Animals; D016380:Brain Tissue Transplantation / Q000379:methods*; D002478:Cells, Cultured; D003714:Denervation; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005333:Fetus; D006085:Graft Survival / Q000235:genetics*; D020439:Growth Cones / Q000378:metabolism / Q000637:transplantation* / Q000648:ultrastructure; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017072:Neostriatum / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*
D019253:Proto-Oncogene Proteins c-bcl-2; D016627:Oxidopamine; D004298:Dopamine