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Transcription factors involved in the pathogenesis of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease.

Cenci Nilsson, Angela LU (2002) In Amino Acids 23(1-3). p.105-109
Abstract
L-DOPA-induced dyskinesia (abnormal involuntary movements) is one of the most debilitating complications of chron-ic L-DOPA pharmacotherapy in Parkinson's disease. It is generally agreed that dyskinesia arises as a consequence of pulsatile dopamine-receptor stimulation in the brain, causing downstream changes in genes and proteins. Advance in our understanding of such changes is critically dependent on the availability of suitable animal models. We have introduced a new method to classify and rate L-DOPA-induced abnormal involuntary movements (AIMs) in 6-hydroxydopamine (6-OHDA) lesioned rats. This method allows us to dissect the molecular correlates of a dyskinetic motor response to L-DOPA in this species. One of the most prominent... (More)
L-DOPA-induced dyskinesia (abnormal involuntary movements) is one of the most debilitating complications of chron-ic L-DOPA pharmacotherapy in Parkinson's disease. It is generally agreed that dyskinesia arises as a consequence of pulsatile dopamine-receptor stimulation in the brain, causing downstream changes in genes and proteins. Advance in our understanding of such changes is critically dependent on the availability of suitable animal models. We have introduced a new method to classify and rate L-DOPA-induced abnormal involuntary movements (AIMs) in 6-hydroxydopamine (6-OHDA) lesioned rats. This method allows us to dissect the molecular correlates of a dyskinetic motor response to L-DOPA in this species. One of the most prominent molecular changes underlying the development of dyskinesia in the rat consists in the striatal induction of prodynorphin gene expression by L-DOPA. This effect is mediated by FosB-related transcription factors of 32-37 kDa, which are co-induced with prodynophin in striatal neurons of the "direct pathway". Both AIM development and the associated upregulation of prodynorphin mRNA by L-DOPA are significantly inhibited by the intrastriatal infusion of fosB antisense. Antisense-mediated knockdown of CREB (cyclic AMP response-element binding proteins) has however no effect. Our results identify fosB as a potential target for adjunctive antiparkinsonian therapies. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Immediate-early genes · Movement disorder · Basal ganglia · Dynorphin · Striatonigral
in
Amino Acids
volume
23
issue
1-3
pages
105 - 109
publisher
Springer
external identifiers
  • wos:000178412200016
  • pmid:12373525
  • scopus:0036389371
ISSN
0939-4451
DOI
10.1007/s00726-001-0116-4
language
English
LU publication?
yes
id
65cde9db-4c99-4d65-83bf-cb33963fccdb (old id 110700)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12373525&dopt=Abstract
date added to LUP
2007-07-11 11:09:45
date last changed
2017-07-30 03:37:30
@article{65cde9db-4c99-4d65-83bf-cb33963fccdb,
  abstract     = {L-DOPA-induced dyskinesia (abnormal involuntary movements) is one of the most debilitating complications of chron-ic L-DOPA pharmacotherapy in Parkinson's disease. It is generally agreed that dyskinesia arises as a consequence of pulsatile dopamine-receptor stimulation in the brain, causing downstream changes in genes and proteins. Advance in our understanding of such changes is critically dependent on the availability of suitable animal models. We have introduced a new method to classify and rate L-DOPA-induced abnormal involuntary movements (AIMs) in 6-hydroxydopamine (6-OHDA) lesioned rats. This method allows us to dissect the molecular correlates of a dyskinetic motor response to L-DOPA in this species. One of the most prominent molecular changes underlying the development of dyskinesia in the rat consists in the striatal induction of prodynorphin gene expression by L-DOPA. This effect is mediated by FosB-related transcription factors of 32-37 kDa, which are co-induced with prodynophin in striatal neurons of the "direct pathway". Both AIM development and the associated upregulation of prodynorphin mRNA by L-DOPA are significantly inhibited by the intrastriatal infusion of fosB antisense. Antisense-mediated knockdown of CREB (cyclic AMP response-element binding proteins) has however no effect. Our results identify fosB as a potential target for adjunctive antiparkinsonian therapies.},
  author       = {Cenci Nilsson, Angela},
  issn         = {0939-4451},
  keyword      = {Immediate-early genes · Movement disorder · Basal ganglia · Dynorphin · Striatonigral},
  language     = {eng},
  number       = {1-3},
  pages        = {105--109},
  publisher    = {Springer},
  series       = {Amino Acids},
  title        = {Transcription factors involved in the pathogenesis of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease.},
  url          = {http://dx.doi.org/10.1007/s00726-001-0116-4},
  volume       = {23},
  year         = {2002},
}