title: Ablation of the subthalamic nucleus protects dopaminergic phenotype but not cell survival in a rat model of Parkinson's disease.
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 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.
authors.affiliation: Department of Neurology, Charité, Humboldt-University of Berlin, Berlin, Germany.
authors.forename: Gesine
authors.initials: G
authors.lastname: Paul
authors.forename: Wassilios
authors.initials: W
authors.lastname: Meissner
authors.forename: Susanne
authors.initials: S
authors.lastname: Rein
authors.forename: Daniel
authors.initials: D
authors.lastname: Harnack
authors.forename: Christine
authors.initials: C
authors.lastname: Winter
authors.forename: Kai
authors.initials: K
authors.lastname: Hosmann
authors.forename: Rudolf
authors.initials: R
authors.lastname: Morgenstern
authors.forename: Andreas
authors.initials: A
authors.lastname: Kupsch
mesh_terms: D000818:Animals; D017115:Catheter Ablation / Q000379:methods*; D002470:Cell Survival / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D020531:Subthalamic Nucleus / Q000166:cytology / Q000378:metabolism / Q000601:surgery*
chemical_list: D004298:Dopamine