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Persistent changes in striatal gene expression induced by long-term L-DOPA treatment in a rat model of Parkinson's disease

Westin, J. E. LU ; Andersson, M.; Lundblad, M. LU and Cenci, M. Angela LU (2001) In European Journal of Neuroscience 14(7). p.1171-1176
Abstract

Current knowledge of the molecular changes induced by dopamine denervation and subsequent treatment with L-DOPA is based on studies performed on relatively acute and young animal models of parkinsonism. It is highly warranted to ask how well these models simulate the state of chronic denervation and sustained L-DOPA pharmacotherapy which are typical of advanced Parkinson's disease. This study investigates the effects of time postdenervation and L-dopa treatment duration on the striatal expression of opioid precursor mRNAs and FosB/DFosB-related proteins. Unilaterally 6-hydroxydopamine-lesioned rats were treated with therapeutical doses of L-DOPA for one year (long-term group) or a few weeks (short-term group). Age-matched lesioned rats... (More)

Current knowledge of the molecular changes induced by dopamine denervation and subsequent treatment with L-DOPA is based on studies performed on relatively acute and young animal models of parkinsonism. It is highly warranted to ask how well these models simulate the state of chronic denervation and sustained L-DOPA pharmacotherapy which are typical of advanced Parkinson's disease. This study investigates the effects of time postdenervation and L-dopa treatment duration on the striatal expression of opioid precursor mRNAs and FosB/DFosB-related proteins. Unilaterally 6-hydroxydopamine-lesioned rats were treated with therapeutical doses of L-DOPA for one year (long-term group) or a few weeks (short-term group). Age-matched lesioned rats received injections of vehicle or bromocriptine, an antiparkinsonian compound which does not produce dyskinesia when administered de novo. The lesion-induced up-regulation of preproenkephalin mRNA expression persisted at more than one year postlesion, and was unaffected by the pharmacological treatments applied. L-DOPA, but not bromocriptine, induced high striatal levels of FosB/DFosB immunoreactivity and prodynorphin mRNA, and these did not differ between short-term and long-term L-DOPA-treated rats. The present data provide the first demonstration that L-DOPA maintains high striatal levels of fosB and prodynorphin gene expression during a prolonged course of treatment, which simulates the clinical practice in Parkinson's disease more closely than the short-treatment paradigms studied thus far.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Chronic FRAs, fosB, Immediate-early genes, Striatonigral, Striatopallidal
in
European Journal of Neuroscience
volume
14
issue
7
pages
6 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:0035783455
ISSN
0953-816X
DOI
10.1046/j.0953-816X.2001.01743.x
language
English
LU publication?
yes
id
edbaad75-307e-48e2-be55-c0253f8a27dd
date added to LUP
2017-04-24 13:04:16
date last changed
2018-01-07 12:00:38
@article{edbaad75-307e-48e2-be55-c0253f8a27dd,
  abstract     = {<p>Current knowledge of the molecular changes induced by dopamine denervation and subsequent treatment with L-DOPA is based on studies performed on relatively acute and young animal models of parkinsonism. It is highly warranted to ask how well these models simulate the state of chronic denervation and sustained L-DOPA pharmacotherapy which are typical of advanced Parkinson's disease. This study investigates the effects of time postdenervation and L-dopa treatment duration on the striatal expression of opioid precursor mRNAs and FosB/DFosB-related proteins. Unilaterally 6-hydroxydopamine-lesioned rats were treated with therapeutical doses of L-DOPA for one year (long-term group) or a few weeks (short-term group). Age-matched lesioned rats received injections of vehicle or bromocriptine, an antiparkinsonian compound which does not produce dyskinesia when administered de novo. The lesion-induced up-regulation of preproenkephalin mRNA expression persisted at more than one year postlesion, and was unaffected by the pharmacological treatments applied. L-DOPA, but not bromocriptine, induced high striatal levels of FosB/DFosB immunoreactivity and prodynorphin mRNA, and these did not differ between short-term and long-term L-DOPA-treated rats. The present data provide the first demonstration that L-DOPA maintains high striatal levels of fosB and prodynorphin gene expression during a prolonged course of treatment, which simulates the clinical practice in Parkinson's disease more closely than the short-treatment paradigms studied thus far.</p>},
  author       = {Westin, J. E. and Andersson, M. and Lundblad, M. and Cenci, M. Angela},
  issn         = {0953-816X},
  keyword      = {Chronic FRAs,fosB,Immediate-early genes,Striatonigral,Striatopallidal},
  language     = {eng},
  number       = {7},
  pages        = {1171--1176},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Neuroscience},
  title        = {Persistent changes in striatal gene expression induced by long-term L-DOPA treatment in a rat model of Parkinson's disease},
  url          = {http://dx.doi.org/10.1046/j.0953-816X.2001.01743.x},
  volume       = {14},
  year         = {2001},
}