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A partial lesion model of Parkinson's disease in mice - Characterization of a 6-OHDA-induced medial forebrain bundle lesion.

Boix, Jordi LU ; Padel, Thomas LU and Paul-Visse, Gesine LU (2015) In Behavioural Brain Research 284(Feb 16). p.196-206
Abstract
The most frequently used animal models for Parkinson's disease (PD) utilize unilateral injection of 6-hydroxydopamine (6-OHDA) in the medial forebrain bundle (MFB), which results in total denervation of the dopaminergic nigrostriatal pathway. However, neuroprotective interventions in PD require models resembling earlier stages of PD, where some dopaminergic cells and fibres remain. The aim of the present study was therefore to establish a MFB partial lesion model in mice. We tested four different 6-OHDA doses, and our results show a dose-dependent loss of nigral dopaminergic cells and striatal fibres that correlated with behavioural impairment in several behavioural tests. Specifically, doses of 0.7μg and 1μg of 6-OHDA induced a partial... (More)
The most frequently used animal models for Parkinson's disease (PD) utilize unilateral injection of 6-hydroxydopamine (6-OHDA) in the medial forebrain bundle (MFB), which results in total denervation of the dopaminergic nigrostriatal pathway. However, neuroprotective interventions in PD require models resembling earlier stages of PD, where some dopaminergic cells and fibres remain. The aim of the present study was therefore to establish a MFB partial lesion model in mice. We tested four different 6-OHDA doses, and our results show a dose-dependent loss of nigral dopaminergic cells and striatal fibres that correlated with behavioural impairment in several behavioural tests. Specifically, doses of 0.7μg and 1μg of 6-OHDA induced a partial denervation of the nigrostriatal pathway, associated with a mild but quantifiable behavioural impairment. We identified the amphetamine-induced rotation, stepping, corridor and cylinder test to be sensitive enough to select partial lesion animals. Based on our data, we proposed a range of cut-off values for these different behavioural tests to select partial lesion mice. Using a statistical prediction model we identified two behavioural tests (the stepping test and amphetamine-induced rotation test) that with a high sensitivity and specificity predict the extent of nigral dopaminergic cell loss and select mice with a partial nigrostriatal lesion prior to further interventions. This model can serve as an important tool to study neuroprotective therapies for PD in mouse models, especially when the treatment targets the substantia nigra and/or striatum. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Behavioural Brain Research
volume
284
issue
Feb 16
pages
196 - 206
publisher
Elsevier
external identifiers
  • pmid:25698603
  • wos:000352672300024
  • scopus:84923319244
ISSN
0166-4328
DOI
10.1016/j.bbr.2015.01.053
language
English
LU publication?
yes
id
ea2c7101-97f6-4d7b-bfea-45d67efa4c80 (old id 5143198)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25698603?dopt=Abstract
date added to LUP
2015-03-09 21:19:11
date last changed
2017-09-17 04:10:19
@article{ea2c7101-97f6-4d7b-bfea-45d67efa4c80,
  abstract     = {The most frequently used animal models for Parkinson's disease (PD) utilize unilateral injection of 6-hydroxydopamine (6-OHDA) in the medial forebrain bundle (MFB), which results in total denervation of the dopaminergic nigrostriatal pathway. However, neuroprotective interventions in PD require models resembling earlier stages of PD, where some dopaminergic cells and fibres remain. The aim of the present study was therefore to establish a MFB partial lesion model in mice. We tested four different 6-OHDA doses, and our results show a dose-dependent loss of nigral dopaminergic cells and striatal fibres that correlated with behavioural impairment in several behavioural tests. Specifically, doses of 0.7μg and 1μg of 6-OHDA induced a partial denervation of the nigrostriatal pathway, associated with a mild but quantifiable behavioural impairment. We identified the amphetamine-induced rotation, stepping, corridor and cylinder test to be sensitive enough to select partial lesion animals. Based on our data, we proposed a range of cut-off values for these different behavioural tests to select partial lesion mice. Using a statistical prediction model we identified two behavioural tests (the stepping test and amphetamine-induced rotation test) that with a high sensitivity and specificity predict the extent of nigral dopaminergic cell loss and select mice with a partial nigrostriatal lesion prior to further interventions. This model can serve as an important tool to study neuroprotective therapies for PD in mouse models, especially when the treatment targets the substantia nigra and/or striatum.},
  author       = {Boix, Jordi and Padel, Thomas and Paul-Visse, Gesine},
  issn         = {0166-4328},
  language     = {eng},
  number       = {Feb 16},
  pages        = {196--206},
  publisher    = {Elsevier},
  series       = {Behavioural Brain Research},
  title        = {A partial lesion model of Parkinson's disease in mice - Characterization of a 6-OHDA-induced medial forebrain bundle lesion.},
  url          = {http://dx.doi.org/10.1016/j.bbr.2015.01.053},
  volume       = {284},
  year         = {2015},
}