Growth and functional efficacy of intrastriatal nigral transplants depend on the extent of nigrostriatal degeneration.
Previous studies have shown that the functional efficacy of intrastriatal transplants of fetal dopamine (DA) neurons in the rat Parkinson model depends on their ability to establish a new functional innervation of the denervated striatum. Here we report that the survival, growth, and function of the grafted DA neurons greatly depend on the severity of the lesion of the host nigrostriatal system. Fiber outgrowth, and to a lesser extent also cell survival, were significantly reduced in animals in which part of the intrinsic DA system was left intact. Moreover, graft-induced functional recovery, as assessed in the stepping, paw-use, and apomorphine rotation tests, was obtained only in severely lesioned animals, i.e., in rats with >70% DA denervation of the host striatum. Functional recovery seen in these animals in which the 6-hydroxydopamine (6-OHDA) lesion was confined to the striatum was more pronounced than that previously obtained in rats with complete lesions of the mesencephalic DA system, indicating that spared portions of the host DA system, particularly those innervating nonstriatal forebrain areas, may be necessary for the grafts to exert their optimal functional effect. These data have implications for the optimal use of fetal nigral transplants in Parkinson patients in different stages of the disease.
Kirik
D
D
Wallenberg Neuroscience Center, Department of Physiological Sciences, Lund University, 22184, Lund, Sweden. Deniz.Kirik@mphy.lu.se
Winkler
C
C
Björklund
A
A
D000818:Animals; D001522:Behavior, Animal; D016380:Brain Tissue Transplantation / Q000379:methods; D002452:Cell Count; D002455:Cell Division; D002470:Cell Survival; D002540:Cerebral Cortex; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D016332:Fetal Tissue Transplantation / Q000379:methods; D006085:Graft Survival; D008032:Limbic System; D009043:Motor Activity; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000196:embryology / Q000201:enzymology / Q000637:transplantation*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase