title: High-frequency stimulation of the subthalamic nucleus counteracts cortical expression of major histocompatibility complex genes in a rat model of Parkinson's disease.
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.
authors.affiliation: Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, 2) Clinic of Neurosurgery, University Medical Center Hamburg-Eppendorf,  Hamburg, Germany; Department of General Psychiatry, Center for Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Grieb
authors.affiliation: Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Engler
authors.affiliation: Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Andrew
authors.initials: A
authors.lastname: Sharott
authors.affiliation: Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: von Nicolai
authors.affiliation: Department of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Streichert
authors.affiliation: Division of General Neurophysiology, Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Ismini
authors.initials: I
authors.lastname: Papageorgiou
authors.affiliation: Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schulte
authors.affiliation: Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Westphal
authors.affiliation: Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Lamszus
authors.affiliation: Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Engel
authors.affiliation: Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Christian K E
authors.initials: CK
authors.lastname: Moll
authors.affiliation: Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hamel
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004599:Electric Stimulation Therapy; D004566:Electrodes; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006649:Histocompatibility Antigens / Q000235:genetics*; D018476:Hypokinesia / Q000150:complications; D008124:Locomotion / Q000187:drug effects; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D066191:Sensorimotor Cortex / Q000378:metabolism* / Q000473:pathology; D020531:Subthalamic Nucleus; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D006649:Histocompatibility Antigens; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase