High-frequency stimulation of the subthalamic nucleus counteracts cortical expression of major histocompatibility complex genes in a rat model of Parkinson’s disease

• Verfasst von: Grieb, Benjamin [VerfasserIn]
• Verfasst von: Papageorgiou, Ismini E. [VerfasserIn]
• Titel: High-frequency stimulation of the subthalamic nucleus counteracts cortical expression of major histocompatibility complex genes in a rat model of Parkinson’s disease
• Verf.angabe: 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
• E-Jahr: 2014
• Jahr: March 12, 2014
• Umfang: 14 S.
• Fussnoten: Gesehen am 05.08.2020
• Titel Quelle: Enthalten in: PLOS ONE
• Ort Quelle: San Francisco, California, US : PLOS, 2006
• Jahr Quelle: 2014
• Band/Heft Quelle: 9(2014,3) Artikel-Nummer e91663, 14 Seiten
• ISSN Quelle: 1932-6203
• DOI: doi:10.1371/journal.pone.0091663
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Functional electrical stimulation
• Sach-SW: Gene expression
• Sach-SW: Gene regulation
• Sach-SW: Major histocompatibility complex
• Sach-SW: Microarrays
• Sach-SW: Parkinson disease
• Sach-SW: Rats
• Sach-SW: Reverse transcriptase-polymerase chain reaction
• K10plus-PPN: 1726241599

Abstract

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.