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Reconstruction of the nigrostriatal dopamine pathway in the adult mouse brain.

Thompson, Lachlan LU ; Grealish, Shane LU ; Kirik, Deniz LU and Björklund, Anders LU (2009) In European Journal of Neuroscience 30(4). p.625-638
Abstract
Transplants of fetal dopamine neurons can be used to restore dopamine neurotransmission in animal models of Parkinson's disease, as well as in patients with advanced Parkinson's disease. In these studies the cells are placed in the striatum rather than in the substantia nigra where they normally reside, which may limit their ability to achieve full restoration of motor function. Using a microtransplantation approach, which allows precise placement of small cell deposits directly into the host substantia nigra, and fetal donor cells that express green fluorescent protein under the control of the tyrosine hydroxylase promoter, we show that dopamine neuroblasts implanted into the substantia nigra of adult mice are capable of generating a new... (More)
Transplants of fetal dopamine neurons can be used to restore dopamine neurotransmission in animal models of Parkinson's disease, as well as in patients with advanced Parkinson's disease. In these studies the cells are placed in the striatum rather than in the substantia nigra where they normally reside, which may limit their ability to achieve full restoration of motor function. Using a microtransplantation approach, which allows precise placement of small cell deposits directly into the host substantia nigra, and fetal donor cells that express green fluorescent protein under the control of the tyrosine hydroxylase promoter, we show that dopamine neuroblasts implanted into the substantia nigra of adult mice are capable of generating a new nigrostriatal pathway with an outgrowth pattern that matches the anatomy of the intrinsic system. This target-directed regrowth was closely aligned with the intrinsic striatonigral fibre projection and further enhanced by over-expression of glial cell line-derived neurotrophic factor in the striatal target. Results from testing of amphetamine-induced rotational behaviour suggest, moreover, that dopamine neurons implanted into the substantia nigra are also capable of integrating into the host circuitry at the functional level. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Neuroscience
volume
30
issue
4
pages
625 - 638
publisher
Wiley-Blackwell
external identifiers
  • wos:000269263500010
  • pmid:19674082
  • scopus:69249109574
ISSN
1460-9568
DOI
10.1111/j.1460-9568.2009.06878.x
language
English
LU publication?
yes
id
cfd852c5-2247-4be0-891f-4906a1337119 (old id 1469837)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19674082?dopt=Abstract
date added to LUP
2009-09-02 15:13:21
date last changed
2017-10-22 04:53:32
@article{cfd852c5-2247-4be0-891f-4906a1337119,
  abstract     = {Transplants of fetal dopamine neurons can be used to restore dopamine neurotransmission in animal models of Parkinson's disease, as well as in patients with advanced Parkinson's disease. In these studies the cells are placed in the striatum rather than in the substantia nigra where they normally reside, which may limit their ability to achieve full restoration of motor function. Using a microtransplantation approach, which allows precise placement of small cell deposits directly into the host substantia nigra, and fetal donor cells that express green fluorescent protein under the control of the tyrosine hydroxylase promoter, we show that dopamine neuroblasts implanted into the substantia nigra of adult mice are capable of generating a new nigrostriatal pathway with an outgrowth pattern that matches the anatomy of the intrinsic system. This target-directed regrowth was closely aligned with the intrinsic striatonigral fibre projection and further enhanced by over-expression of glial cell line-derived neurotrophic factor in the striatal target. Results from testing of amphetamine-induced rotational behaviour suggest, moreover, that dopamine neurons implanted into the substantia nigra are also capable of integrating into the host circuitry at the functional level.},
  author       = {Thompson, Lachlan and Grealish, Shane and Kirik, Deniz and Björklund, Anders},
  issn         = {1460-9568},
  language     = {eng},
  number       = {4},
  pages        = {625--638},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Neuroscience},
  title        = {Reconstruction of the nigrostriatal dopamine pathway in the adult mouse brain.},
  url          = {http://dx.doi.org/10.1111/j.1460-9568.2009.06878.x},
  volume       = {30},
  year         = {2009},
}