Subthalamic nucleus lesioning inhibits expression and phosphorylation of c-Jun in nigral neurons in the rat’s 6-OHDA model of Parkinson’s disease
Synapse. 2006-01-01; 60(1): 69-80
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1. Synapse. 2006 Jul;60(1):69-80.
Subthalamic nucleus lesioning inhibits expression and phosphorylation of c-Jun in
nigral neurons in the rat’s 6-OHDA model of Parkinson’s disease.
Winter C(1), Hosmann K, Harnack D, Meissner W, Paul G, Morgenstern R, Kupsch A.
(1)Department of Neurology, Charité-University Medicine Berlin, Campus Charité
Mitte, Berlin, Germany.
Parkinson’s Disease (PD) is characterized by a loss of nigral dopamine (DA)
neurons, followed by a striatal DA deficit. Inhibition of the subthalamic nucleus
(STN) reverses L-DOPA sensitive motor symptoms and improves efficacy of
pharmacotherapy in PD-patients. The underlying mechanism of these effects,
however, remains largely unknown. Previously, we could show in the rat’s
6-hydroxyDA (6-OHDA) model of PD that ablative STN-lesioning exerts functionally
neuroprotective effects on the DAergic nigrostriatal pathway against 6-OHDA
toxicity, in terms of elevating the number of tyrosine hydroxylase
(TH)-expressing neurons rather than enhancing the total number of cells surviving
2 and 6 weeks post lesioning, as assessed via fluorogold staining. These data
were correlated with increased functional recovery of 6-OHDA-lesioned rats with
preceding STN-lesioning. Here, we extend the previous study design to observation
periods of up to 12 weeks to assess long-term effects. Furthermore, to elucidate
cellular mechanisms underlying potential neuroprotective effects, we explore the
regulation of cellular markers involved in neurodegenerative cascades via
immunocytochemistry. We show that preceding STN-lesioning significantly inhibits
6-OHDA induced expression/phosphorylation of the transcription factor c-Jun in
surviving nigral neurons in comparison with controls. However, we also
demonstrate that functionally neuroprotective effects of preceding STN-lesioning
subside after 12 weeks, as assessed with TH immunostaining. We therefore conclude
that c-Jun induction/phosphorylation is involved in 6-OHDA toxicity and that
STN-lesioning transiently preserves of dopaminergic phenotype of nigral neurons
partially via delaying the induction and attenuating the expression and
phosphorylation of c-Jun.
(c) 2006 Wiley-Liss, Inc.
PMID: 16598703 [Indexed for MEDLINE]