High-Frequency Stimulation of the Subthalamic Nucleus Counteracts Cortical Expression of Major Histocompatibility Complex Genes in a Rat Model of Parkinson’s Disease

نویسندگان

  • 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
چکیده

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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Correction: High-Frequency Stimulation of the Subthalamic Nucleus Counteracts Cortical Expression of Major Histocompatibility Complex Genes in a Rat Model of Parkinson’s Disease

Copyright: ß 2014 The PLOS ONE Staff. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Reply to Letter to the Editor

[3] Hershey T, Revilla FJ, Wernle AR, McGee-Minnich L, Antenor JV, Videen TO, et al. Cortical and subcortical blood flow effects of subthalamic nucleus stimulation in PD. Neurology 2003;61:816e21. [4] Haslinger B, Kalteis K, Boecker H, Alesch F, Ceballos-Baumann AO. Frequency-correlated decreases of motor cortex activity associated with subthalamic nucleus stimulation in Parkinson’s disease. Ne...

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عنوان ژورنال:

دوره 9  شماره 

صفحات  -

تاریخ انتشار 2014