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Investigating the molecular mechanisms of L-DOPA-induced dyskinesia in the mouse

Francardo, Veronica LU and Cenci, M. Angela LU (2014) In Parkinsonism and Related Disorders 20(SUPPL.1). p.20-22
Abstract

L-DOPA-induced dyskinesia (LID) is a major complication of the pharmacotherapy of Parkinson's disease (PD). Animal models of LID are essential for investigating pathogenic pathways and therapeutic targets. While non-human primates have been the preferred species for pathophysiological studies, mouse models of LID have been recently produced and characterized to facilitate molecular investigations. Most of these studies have used mice with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal projection sustaining treatment with L-DOPA for 1-4 weeks. Mice with complete medial forebrain bundle lesions have been found to develop dyskinetic movements of maximal severity associated with a pronounced post-synaptic... (More)

L-DOPA-induced dyskinesia (LID) is a major complication of the pharmacotherapy of Parkinson's disease (PD). Animal models of LID are essential for investigating pathogenic pathways and therapeutic targets. While non-human primates have been the preferred species for pathophysiological studies, mouse models of LID have been recently produced and characterized to facilitate molecular investigations. Most of these studies have used mice with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal projection sustaining treatment with L-DOPA for 1-4 weeks. Mice with complete medial forebrain bundle lesions have been found to develop dyskinetic movements of maximal severity associated with a pronounced post-synaptic supersensitivity of D1-receptor dependent signaling pathways throughout the striatum. In contrast, mice with striatal 6-OHDA lesions have been found to exhibit a variable susceptibility to LID and a regionally restricted post-synaptic supersensitivity. Genetic mouse models of PD have just started to be used for studies of LID, providing an opportunity to dissect the impact of genetic factors on the maladaptive neuroplasticity that drives the development of treatment-induced involuntary movements in PD.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animal models, Dopamine replacement therapy, Genetic models, Motor complications, Striatum
in
Parkinsonism and Related Disorders
volume
20
issue
SUPPL.1
pages
20 - 22
publisher
Elsevier
external identifiers
  • scopus:84887971792
ISSN
1353-8020
DOI
10.1016/S1353-8020(13)70008-7
language
English
LU publication?
yes
id
c07d1d69-ebdf-4e66-ae3f-b25b5121ea51
date added to LUP
2017-04-24 12:48:15
date last changed
2017-04-24 12:48:15
@article{c07d1d69-ebdf-4e66-ae3f-b25b5121ea51,
  abstract     = {<p>L-DOPA-induced dyskinesia (LID) is a major complication of the pharmacotherapy of Parkinson's disease (PD). Animal models of LID are essential for investigating pathogenic pathways and therapeutic targets. While non-human primates have been the preferred species for pathophysiological studies, mouse models of LID have been recently produced and characterized to facilitate molecular investigations. Most of these studies have used mice with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal projection sustaining treatment with L-DOPA for 1-4 weeks. Mice with complete medial forebrain bundle lesions have been found to develop dyskinetic movements of maximal severity associated with a pronounced post-synaptic supersensitivity of D1-receptor dependent signaling pathways throughout the striatum. In contrast, mice with striatal 6-OHDA lesions have been found to exhibit a variable susceptibility to LID and a regionally restricted post-synaptic supersensitivity. Genetic mouse models of PD have just started to be used for studies of LID, providing an opportunity to dissect the impact of genetic factors on the maladaptive neuroplasticity that drives the development of treatment-induced involuntary movements in PD.</p>},
  author       = {Francardo, Veronica and Cenci, M. Angela},
  issn         = {1353-8020},
  keyword      = {Animal models,Dopamine replacement therapy,Genetic models,Motor complications,Striatum},
  language     = {eng},
  number       = {SUPPL.1},
  pages        = {20--22},
  publisher    = {Elsevier},
  series       = {Parkinsonism and Related Disorders},
  title        = {Investigating the molecular mechanisms of L-DOPA-induced dyskinesia in the mouse},
  url          = {http://dx.doi.org/10.1016/S1353-8020(13)70008-7},
  volume       = {20},
  year         = {2014},
}