Enhancement of graft survival and sensorimotor behavioral recovery in rats undergoing transplantation with dopaminergic cells exposed to glial cell line-derived neurotrophic factor.
OBJECTIVE
The goal of this study was to investigate the ability of fetal dopaminergic neurons to improve complex sensorimotor behavior.


METHODS
The authors obtained ventral mesencephalic tissue from 14-day-old rat fetuses. The cells were exposed to glial cell line-derived neurotrophic factor (GDNF) prior to transplantation into rats with unilateral 6-hydroxydopamine lesions of the dopaminergic nigrostriatal pathway. Animals that received 400,000 cells exposed to GDNF demonstrated significant improvement in contralateral forelimb function and showed improvement in rotational behavior faster than animals that received cells not exposed to GDNF. Increasing the number of implanted cells to 800,000 exposed to GDNF did not result in any additional improvement in functional recovery.


CONCLUSIONS
As neural grafting procedures in the nervous system evolve and genetically engineered cells or stem cells replace fetal tissue, crucial questions about cell number and trophic regulation will need to be addressed. This study demonstrates that grafting of 400,000 cells exposed to GDNF before transplantation has a beneficial effect in the restoration of complex sensorimotor behavior.
Mehta
V
V
Department of Surgery, Dalhousie University, Halifax, Nova Scotia, Canada.
Hong
M
M
Spears
J
J
Mendez
I
I
D018663:Adrenergic Agents / Q000009:adverse effects; D000320:Adrenergic Fibers / Q000473:pathology / Q000637:transplantation; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016380:Brain Tissue Transplantation / Q000473:pathology; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D016332:Fetal Tissue Transplantation / Q000473:pathology; D005552:Forelimb / Q000502:physiology; D006085:Graft Survival / Q000187:drug effects; D008636:Mesencephalon / Q000196:embryology / Q000637:transplantation*; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D009419:Nerve Tissue Proteins / Q000627:therapeutic use*; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000473:pathology / Q000637:transplantation; D016627:Oxidopamine / Q000009:adverse effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000601:surgery; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012399:Rotation; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology; D014021:Tissue Preservation
D018663:Adrenergic Agents; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016627:Oxidopamine