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Ablation of the subthalamic nucleus protects dopaminergic phenotype but not cell survival in a rat model of Parkinson's disease

Paul, Gesine LU ; Meissner, Wassilios G.; Rein, Susanne; Harnack, Daniel; Winter, Christine; Hosmann, Kai; Morgenstern, Rudolf and Kupsch, Andreas (2004) In Experimental Neurology 185(2). p.272-280
Abstract

Inhibition or ablation of the hyperactive subthalamic nucleus (STN) in Parkinson's disease (PD) does not only reverse motor deficits, silencing the glutamatergic output of the subthalamic nucleus, but has also been implicated to have neuroprotective effects on nigral neurons in animal models of Parkinson's disease. Ablation of the subthalamic nucleus has been shown to increase the number of tyrosinhydroxylase-immunopositive cells and partially restores behavioral deficits in animal models of Parkinson's disease. However, it is unclear whether subthalamic nucleus ablation indeed prevents cell death or whether the effect is due to the rescue of the dopaminergic (DA) phenotype of impaired cells by upregulating tyrosine hydroxylase (TH). We... (More)

Inhibition or ablation of the hyperactive subthalamic nucleus (STN) in Parkinson's disease (PD) does not only reverse motor deficits, silencing the glutamatergic output of the subthalamic nucleus, but has also been implicated to have neuroprotective effects on nigral neurons in animal models of Parkinson's disease. Ablation of the subthalamic nucleus has been shown to increase the number of tyrosinhydroxylase-immunopositive cells and partially restores behavioral deficits in animal models of Parkinson's disease. However, it is unclear whether subthalamic nucleus ablation indeed prevents cell death or whether the effect is due to the rescue of the dopaminergic (DA) phenotype of impaired cells by upregulating tyrosine hydroxylase (TH). We therefore investigated the potential neuroprotective effects of a preceding subthalamic nucleus lesion on 6-hydroxydopamine (6-OHDA)-induced nigral cell death and compared the retrograde tracer fluorogold (FG) as a marker of cell survival with tyrosinhydroxylase immunoreactivity as a marker of the dopaminergic phenotype. In the present study, we show that ablation of the subthalamic nucleus does not affect the number of fluorogold-labeled cells but increases the number of tyrosinhydroxylase-positive neurons in subthalamic nucleus-lesioned hemiparkinsonian animals and leads to partial behavioral recovery of the rats. We conclude that subthalamic nucleus ablation exerts neuroprotective properties on the dopaminergic nigrostriatal pathway against 6-hydroxydopamine toxicity in terms of rescuing the neurotransmitter phenotype in the remaining neurons rather than enhancing the total number of nigral cells.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
6-Hydroxydopamine, Fluorogold, Parkinson's disease, Subthalamic nucleus, Tyrosine hydroxylase
in
Experimental Neurology
volume
185
issue
2
pages
9 pages
publisher
Academic Press
external identifiers
  • scopus:0346374579
ISSN
0014-4886
DOI
10.1016/S0014-4886(03)00363-7
language
English
LU publication?
no
id
aa370552-9f56-4ff8-9bba-800c7b760a49
date added to LUP
2017-05-18 12:52:21
date last changed
2017-10-22 05:30:48
@article{aa370552-9f56-4ff8-9bba-800c7b760a49,
  abstract     = {<p>Inhibition or ablation of the hyperactive subthalamic nucleus (STN) in Parkinson's disease (PD) does not only reverse motor deficits, silencing the glutamatergic output of the subthalamic nucleus, but has also been implicated to have neuroprotective effects on nigral neurons in animal models of Parkinson's disease. Ablation of the subthalamic nucleus has been shown to increase the number of tyrosinhydroxylase-immunopositive cells and partially restores behavioral deficits in animal models of Parkinson's disease. However, it is unclear whether subthalamic nucleus ablation indeed prevents cell death or whether the effect is due to the rescue of the dopaminergic (DA) phenotype of impaired cells by upregulating tyrosine hydroxylase (TH). We therefore investigated the potential neuroprotective effects of a preceding subthalamic nucleus lesion on 6-hydroxydopamine (6-OHDA)-induced nigral cell death and compared the retrograde tracer fluorogold (FG) as a marker of cell survival with tyrosinhydroxylase immunoreactivity as a marker of the dopaminergic phenotype. In the present study, we show that ablation of the subthalamic nucleus does not affect the number of fluorogold-labeled cells but increases the number of tyrosinhydroxylase-positive neurons in subthalamic nucleus-lesioned hemiparkinsonian animals and leads to partial behavioral recovery of the rats. We conclude that subthalamic nucleus ablation exerts neuroprotective properties on the dopaminergic nigrostriatal pathway against 6-hydroxydopamine toxicity in terms of rescuing the neurotransmitter phenotype in the remaining neurons rather than enhancing the total number of nigral cells.</p>},
  author       = {Paul, Gesine and Meissner, Wassilios G. and Rein, Susanne and Harnack, Daniel and Winter, Christine and Hosmann, Kai and Morgenstern, Rudolf and Kupsch, Andreas},
  issn         = {0014-4886},
  keyword      = {6-Hydroxydopamine,Fluorogold,Parkinson's disease,Subthalamic nucleus,Tyrosine hydroxylase},
  language     = {eng},
  number       = {2},
  pages        = {272--280},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Ablation of the subthalamic nucleus protects dopaminergic phenotype but not cell survival in a rat model of Parkinson's disease},
  url          = {http://dx.doi.org/10.1016/S0014-4886(03)00363-7},
  volume       = {185},
  year         = {2004},
}