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The A9 dopamine neuron component in grafts of ventral mesencephalon is an important determinant for recovery of motor function in a rat model of Parkinson's disease

Grealish, Shane LU ; Jönsson, Marie LU ; Li, Meng; Kirik, Deniz LU ; Björklund, Anders LU and Thompson, Lachlan LU (2010) In Brain 133. p.482-495
Abstract
Grafts of foetal ventral mesencephalon, used in cell replacement therapy for Parkinson's disease, are known to contain a mix of dopamine neuronal subtypes including the A9 neurons of the substantia nigra and the A10 neurons of the ventral tegmental area. However, the relative importance of these subtypes for functional repair of the brain affected by Parkinson's disease has not been studied thoroughly. Here, we report results from a series of grafting experiments where the anatomical and functional properties of grafts either selectively lacking in A9 neurons, or with a typical A9/A10 composition were compared. The results show that the A9 component of intrastriatal grafts is of critical importance for recovery in tests on motor... (More)
Grafts of foetal ventral mesencephalon, used in cell replacement therapy for Parkinson's disease, are known to contain a mix of dopamine neuronal subtypes including the A9 neurons of the substantia nigra and the A10 neurons of the ventral tegmental area. However, the relative importance of these subtypes for functional repair of the brain affected by Parkinson's disease has not been studied thoroughly. Here, we report results from a series of grafting experiments where the anatomical and functional properties of grafts either selectively lacking in A9 neurons, or with a typical A9/A10 composition were compared. The results show that the A9 component of intrastriatal grafts is of critical importance for recovery in tests on motor performance, in a rodent model of Parkinson's disease. Analysis at the histological level indicates that this is likely to be due to the unique ability of A9 neurons to innervate and functionally activate their target structure, the dorsolateral region of the host striatum. The findings highlight dopamine neuronal subtype composition as a potentially important parameter to monitor in order to understand the variable nature of functional outcome better in transplantation studies. Furthermore, the results have interesting implications for current efforts in this field to generate well-characterized and standardized preparations of transplantable dopamine neuronal progenitors from stem cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
striatal innervation, ventral tegmental, substantia nigra, transplantation, cell therapy, connectivity, Pitx3
in
Brain
volume
133
pages
482 - 495
publisher
Oxford University Press
external identifiers
  • wos:000274777700014
  • scopus:77249086109
ISSN
1460-2156
DOI
10.1093/brain/awp328
language
English
LU publication?
yes
id
9f5b465a-e4a0-45bf-af57-09da2d23c87d (old id 1568317)
date added to LUP
2010-03-23 13:23:20
date last changed
2018-05-29 10:25:54
@article{9f5b465a-e4a0-45bf-af57-09da2d23c87d,
  abstract     = {Grafts of foetal ventral mesencephalon, used in cell replacement therapy for Parkinson's disease, are known to contain a mix of dopamine neuronal subtypes including the A9 neurons of the substantia nigra and the A10 neurons of the ventral tegmental area. However, the relative importance of these subtypes for functional repair of the brain affected by Parkinson's disease has not been studied thoroughly. Here, we report results from a series of grafting experiments where the anatomical and functional properties of grafts either selectively lacking in A9 neurons, or with a typical A9/A10 composition were compared. The results show that the A9 component of intrastriatal grafts is of critical importance for recovery in tests on motor performance, in a rodent model of Parkinson's disease. Analysis at the histological level indicates that this is likely to be due to the unique ability of A9 neurons to innervate and functionally activate their target structure, the dorsolateral region of the host striatum. The findings highlight dopamine neuronal subtype composition as a potentially important parameter to monitor in order to understand the variable nature of functional outcome better in transplantation studies. Furthermore, the results have interesting implications for current efforts in this field to generate well-characterized and standardized preparations of transplantable dopamine neuronal progenitors from stem cells.},
  author       = {Grealish, Shane and Jönsson, Marie and Li, Meng and Kirik, Deniz and Björklund, Anders and Thompson, Lachlan},
  issn         = {1460-2156},
  keyword      = {striatal innervation,ventral tegmental,substantia nigra,transplantation,cell therapy,connectivity,Pitx3},
  language     = {eng},
  pages        = {482--495},
  publisher    = {Oxford University Press},
  series       = {Brain},
  title        = {The A9 dopamine neuron component in grafts of ventral mesencephalon is an important determinant for recovery of motor function in a rat model of Parkinson's disease},
  url          = {http://dx.doi.org/10.1093/brain/awp328},
  volume       = {133},
  year         = {2010},
}