GDNF enhances dopaminergic cell survival and fibre outgrowth in embryonic nigral grafts.
Two groups of rats with unilateral 6OHDA lesions received either intrastriatal suspension grafts of embryonic ventral mesencephalon or sham grafts. Three subgroups of each of these received intrastriatal infusions of 1000 ng or 500 ng glial cell-line derived trophic factor (GDNF) or vehicle alone for 10 consecutive days. There was a highly significant dose-dependent effect of GDNF both on the number of TH-positive cells surviving in the grafts and on the density of fibre outgrowth. All grafted rats showed rapid compensation of amphetamine-induced rotation compared with rats with sham grafts. GDNF may provide a powerful tool to enhance the survival and maturation of dopaminergic neurones within mesencephalic transplants.
Sinclair
S R
SR
MRC Cambridge Centre for Brain Repair, University of Cambridge, UK.
Svendsen
C N
CN
Torres
E M
EM
Martin
D
D
Fawcett
J W
JW
Dunnett
S B
SB
D000818:Animals; D016380:Brain Tissue Transplantation; D002470:Cell Survival / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects*
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D004298:Dopamine