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Growth and functional efficacy of intrastriatal nigral transplants depend on the extent of nigrostriatal degeneration

Kirik, Deniz LU ; Winkler, Christian LU and Björklund, Anders LU (2001) In The Journal of neuroscience : the official journal of the Society for Neuroscience 21(8). p.2889-2896
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Parkinson's disease, 6-hydroxydopamine, transplantation, sensorimotor behavior, stepping, paw use, tyrosine hydroxylase, stereology
in
The Journal of neuroscience : the official journal of the Society for Neuroscience
volume
21
issue
8
pages
2889 - 2896
publisher
Society for Neuroscience
external identifiers
  • pmid:11306640
  • scopus:0035871386
ISSN
1529-2401
language
English
LU publication?
yes
id
722549ac-0c91-4a10-be40-3185c050b0bc (old id 1122822)
alternative location
http://www.jneurosci.org/cgi/reprint/21/8/2889
date added to LUP
2008-07-01 14:02:14
date last changed
2018-05-29 12:10:22
@article{722549ac-0c91-4a10-be40-3185c050b0bc,
  abstract     = {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.},
  author       = {Kirik, Deniz and Winkler, Christian and Björklund, Anders},
  issn         = {1529-2401},
  keyword      = {Parkinson's disease,6-hydroxydopamine,transplantation,sensorimotor behavior,stepping,paw use,tyrosine hydroxylase,stereology},
  language     = {eng},
  number       = {8},
  pages        = {2889--2896},
  publisher    = {Society for Neuroscience},
  series       = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
  title        = {Growth and functional efficacy of intrastriatal nigral transplants depend on the extent of nigrostriatal degeneration},
  volume       = {21},
  year         = {2001},
}