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Characterisation of behavioural and neurodegenerative changes induced by intranigral 6-hydroxydopamine lesions in a mouse model of Parkinson's disease.

Grealish, Shane LU ; Mattsson, Bengt LU ; Draxler, Peter LU and Björklund, Anders LU (2010) In European Journal of Neuroscience Jul 1. p.2266-2278
Abstract
Abstract Despite the widespread use of mice as models of Parkinson's disease there is a surprising lack of validation and characterisation of unilateral lesion models in mice and the extent of behavioural impairments induced by such lesions. The aim of the present study was to characterise the behavioural deficits observed after injection of 6-hydroxydopamine unilaterally into the substantia nigra, and correlate the behavioural impairments with the extent of damage to the mesostriatal dopaminergic pathway. We found that a recently introduced test for assessment of sensorimotor impairment, the corridor task, was particularly useful in determining lesion severity, and that this test, in combination with standard drug-induced rotation tests,... (More)
Abstract Despite the widespread use of mice as models of Parkinson's disease there is a surprising lack of validation and characterisation of unilateral lesion models in mice and the extent of behavioural impairments induced by such lesions. The aim of the present study was to characterise the behavioural deficits observed after injection of 6-hydroxydopamine unilaterally into the substantia nigra, and correlate the behavioural impairments with the extent of damage to the mesostriatal dopaminergic pathway. We found that a recently introduced test for assessment of sensorimotor impairment, the corridor task, was particularly useful in determining lesion severity, and that this test, in combination with standard drug-induced rotation tests, can be used to select animals with profound (>/= 80%) dopaminergic lesions that are stable over time. Based on these data we propose criteria that can be used to predict the extent of lesion, classified as severe, intermediate or mild lesions of the mesostriatal pathway. The correlation of cell loss and striatal innervation with the performance in each test provides a useful tool for the assessment of functional recovery in neurorestoration and cell transplantation studies, and for the evaluation of the in vivo efficacy and performance of stem cell-derived dopamine neuron preparations. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Neuroscience
volume
Jul 1
pages
2266 - 2278
publisher
Wiley-Blackwell
external identifiers
  • wos:000279021600014
  • pmid:20529122
  • scopus:77953800114
ISSN
1460-9568
DOI
10.1111/j.1460-9568.2010.07265.x
language
English
LU publication?
yes
id
3b1b980f-e0cb-418c-aeb9-f72a83da9f6d (old id 1626301)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20529122?dopt=Abstract
date added to LUP
2010-07-05 10:03:01
date last changed
2018-07-15 04:18:07
@article{3b1b980f-e0cb-418c-aeb9-f72a83da9f6d,
  abstract     = {Abstract Despite the widespread use of mice as models of Parkinson's disease there is a surprising lack of validation and characterisation of unilateral lesion models in mice and the extent of behavioural impairments induced by such lesions. The aim of the present study was to characterise the behavioural deficits observed after injection of 6-hydroxydopamine unilaterally into the substantia nigra, and correlate the behavioural impairments with the extent of damage to the mesostriatal dopaminergic pathway. We found that a recently introduced test for assessment of sensorimotor impairment, the corridor task, was particularly useful in determining lesion severity, and that this test, in combination with standard drug-induced rotation tests, can be used to select animals with profound (>/= 80%) dopaminergic lesions that are stable over time. Based on these data we propose criteria that can be used to predict the extent of lesion, classified as severe, intermediate or mild lesions of the mesostriatal pathway. The correlation of cell loss and striatal innervation with the performance in each test provides a useful tool for the assessment of functional recovery in neurorestoration and cell transplantation studies, and for the evaluation of the in vivo efficacy and performance of stem cell-derived dopamine neuron preparations.},
  author       = {Grealish, Shane and Mattsson, Bengt and Draxler, Peter and Björklund, Anders},
  issn         = {1460-9568},
  language     = {eng},
  pages        = {2266--2278},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Neuroscience},
  title        = {Characterisation of behavioural and neurodegenerative changes induced by intranigral 6-hydroxydopamine lesions in a mouse model of Parkinson's disease.},
  url          = {http://dx.doi.org/10.1111/j.1460-9568.2010.07265.x},
  volume       = {Jul 1},
  year         = {2010},
}