Advanced

High dose levodopa therapy is not toxic in multiple system atrophy: Experimental evidence

Stefanova, Nadia; Kollensperger, Martin; Hainzer, Monika; Cenci Nilsson, Angela LU ; Poewe, Werner and Wenning, Gregor Karl (2007) In Movement Disorders 27(7). p.969-973
Abstract
Levodopa is generally regarded the first choice therapy for parkinsonism associated with multiple system atrophy (MSA-P). However, MSA-P patients often show a poor or unsustained levodopa response which inflicts high dose therapy. This is generally attributed to progressive striatal degeneration with loss of dopamine receptors. Experimental evidence suggests that dopaminergic stimulation may accelerate the striatal disease process in MSA, possibly by pro-oxidative mechanisms. Intact nigrostriatal dopamine release augments striatal lesion size in the unilateral nigral and striatal double lesion rat model of MSA-P. Further, neuronal vulnerability to exogenous oxidative stress is increased in a transgenic MSA mouse model with oligodendroglial... (More)
Levodopa is generally regarded the first choice therapy for parkinsonism associated with multiple system atrophy (MSA-P). However, MSA-P patients often show a poor or unsustained levodopa response which inflicts high dose therapy. This is generally attributed to progressive striatal degeneration with loss of dopamine receptors. Experimental evidence suggests that dopaminergic stimulation may accelerate the striatal disease process in MSA, possibly by pro-oxidative mechanisms. Intact nigrostriatal dopamine release augments striatal lesion size in the unilateral nigral and striatal double lesion rat model of MSA-P. Further, neuronal vulnerability to exogenous oxidative stress is increased in a transgenic MSA mouse model with oligodendroglial alpha-synuclein inclusions. The aim of the present study was to analyze whether high dose levodopa delivery in the transgenic MSA model is associated with neurotoxicity exacerbated by the presence of oligodendroglial alpha-synuclein inclusion pathology. Control and transgenic MSA mice underwent pulsatile treatment with either vehicle, low or high dose levodopa for a period of 1 month. Behavioral and neuropathological indices failed to show evidence for neurotoxic effects of high-dose levodopa in this alpha-synuclein transgenic MSA model. These findings support the idea that high dose levodopa therapy in MSA is not detrimental to the underlying neuropathological process. (C) 2007 Movement Disorder Society. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
levodopa, neurodegeneration, glial cytoplasmic inclusions, alpha-synuclein, multiple system atrophy, transgenic mouse
in
Movement Disorders
volume
27
issue
7
pages
969 - 973
publisher
John Wiley & Sons
external identifiers
  • wos:000246917000010
  • scopus:34347215900
ISSN
0885-3185
DOI
10.1002/mds.21468
language
English
LU publication?
yes
id
9e5ef041-989f-4722-9f22-e85c133d1244 (old id 660446)
date added to LUP
2007-12-20 11:52:12
date last changed
2017-01-01 05:00:17
@article{9e5ef041-989f-4722-9f22-e85c133d1244,
  abstract     = {Levodopa is generally regarded the first choice therapy for parkinsonism associated with multiple system atrophy (MSA-P). However, MSA-P patients often show a poor or unsustained levodopa response which inflicts high dose therapy. This is generally attributed to progressive striatal degeneration with loss of dopamine receptors. Experimental evidence suggests that dopaminergic stimulation may accelerate the striatal disease process in MSA, possibly by pro-oxidative mechanisms. Intact nigrostriatal dopamine release augments striatal lesion size in the unilateral nigral and striatal double lesion rat model of MSA-P. Further, neuronal vulnerability to exogenous oxidative stress is increased in a transgenic MSA mouse model with oligodendroglial alpha-synuclein inclusions. The aim of the present study was to analyze whether high dose levodopa delivery in the transgenic MSA model is associated with neurotoxicity exacerbated by the presence of oligodendroglial alpha-synuclein inclusion pathology. Control and transgenic MSA mice underwent pulsatile treatment with either vehicle, low or high dose levodopa for a period of 1 month. Behavioral and neuropathological indices failed to show evidence for neurotoxic effects of high-dose levodopa in this alpha-synuclein transgenic MSA model. These findings support the idea that high dose levodopa therapy in MSA is not detrimental to the underlying neuropathological process. (C) 2007 Movement Disorder Society.},
  author       = {Stefanova, Nadia and Kollensperger, Martin and Hainzer, Monika and Cenci Nilsson, Angela and Poewe, Werner and Wenning, Gregor Karl},
  issn         = {0885-3185},
  keyword      = {levodopa,neurodegeneration,glial cytoplasmic inclusions,alpha-synuclein,multiple system atrophy,transgenic mouse},
  language     = {eng},
  number       = {7},
  pages        = {969--973},
  publisher    = {John Wiley & Sons},
  series       = {Movement Disorders},
  title        = {High dose levodopa therapy is not toxic in multiple system atrophy: Experimental evidence},
  url          = {http://dx.doi.org/10.1002/mds.21468},
  volume       = {27},
  year         = {2007},
}