High-frequency stimulation of the subthalamic nucleus counteracts cortical expression of major histocompatibility complex genes in a rat model of Parkinson’s disease
High-frequency stimulation of the subthalamic nucleus (STN-HFS) is widely used as therapeutic intervention in patients suffering from advanced Parkinson’s disease. STN-HFS exerts a powerful modulatory effect on cortical motor control by orthodromic modulation of basal ganglia outflow and via antidro...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
March 12, 2014
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| In: |
PLOS ONE
Year: 2014, Volume: 9, Issue: 3 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0091663 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1371/journal.pone.0091663 Verlag, lizenzpflichtig, Volltext: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0091663 
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| Author Notes: | Benjamin Grieb, Gerhard Engler, Andrew Sharott, Constantin von Nicolai, Thomas Streichert, Ismini Papageorgiou, Alexander Schulte, Manfred Westphal, Katrin Lamszus, Andreas K. Engel, Christian K. E. Moll, Wolfgang Hamel |
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| 520 | |a High-frequency stimulation of the subthalamic nucleus (STN-HFS) is widely used as therapeutic intervention in patients suffering from advanced Parkinson’s disease. STN-HFS exerts a powerful modulatory effect on cortical motor control by orthodromic modulation of basal ganglia outflow and via antidromic activation of corticofugal fibers. However, STN-HFS-induced changes of the sensorimotor cortex are hitherto unexplored. To address this question at a genomic level, we performed mRNA expression analyses using Affymetrix microarray gene chips and real-time RT-PCR in sensorimotor cortex of parkinsonian and control rats following STN-HFS. Experimental parkinsonism was induced in Brown Norway rats by bilateral nigral injections of 6-hydroxydopamine and was assessed histologically, behaviorally, and electrophysiologically. We applied prolonged (23h) unilateral STN-HFS in awake and freely moving animals, with the non-stimulated hemisphere serving as an internal control for gene expression analyses. Gene enrichment analysis revealed strongest regulation in major histocompatibility complex (MHC) related genes. STN-HFS led to a cortical downregulation of several MHC class II (RT1-Da, Db1, Ba, and Cd74) and MHC class I (RT1CE) encoding genes. The same set of genes showed increased expression levels in a comparison addressing the effect of 6-hydroxydopamine lesioning. Hence, our data suggest the possible association of altered microglial activity and synaptic transmission by STN-HFS within the sensorimotor cortex of 6-hydroxydopamine treated rats. | ||
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