Impact of chronic subthalamic high-frequency stimulation on metabolic basal ganglia activity: a 2-deoxyglucose uptake and cytochrome oxidase mRNA study in a macaque model of Parkinson's disease

The mechanisms of action of high‐frequency stimulation (HFS) of the subthalamic nucleus (STN) remain only partially understood. Hitherto, experimental studies have suggested that STN‐HFS reduces the activity of STN neurons. However, some recent reports have challenged this view, showing that STN‐HFS...

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Vydané v:	The European journal of neuroscience Ročník 25; číslo 5; s. 1492 - 1500
Hlavní autori:	Meissner, Wassilios, Guigoni, Celine, Cirilli, Laetitia, Garret, Maurice, Bioulac, Bernard H., Gross, Christian E., Bezard, Erwan, Benazzouz, Abdelhamid
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Oxford, UK Blackwell Publishing Ltd 01.03.2007
Predmet:	Animals basal ganglia Basal Ganglia - metabolism deep brain stimulation Deoxyglucose - metabolism Disease Models, Animal Dose-Response Relationship, Radiation Electric Stimulation Therapy - methods Electron Transport Complex IV - genetics Electron Transport Complex IV - metabolism Female Gene Expression Regulation - radiation effects globus pallidus internalis Macaca Macaca fascicularis motor thalamus Parkinsonian Disorders - metabolism Parkinsonian Disorders - pathology Parkinsonian Disorders - surgery Primates RNA, Messenger - metabolism Statistics, Nonparametric STN subthalamic nucleus Subthalamic Nucleus - physiopathology Subthalamic Nucleus - radiation effects
ISSN:	0953-816X, 1460-9568
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Shrnutí:	The mechanisms of action of high‐frequency stimulation (HFS) of the subthalamic nucleus (STN) remain only partially understood. Hitherto, experimental studies have suggested that STN‐HFS reduces the activity of STN neurons. However, some recent reports have challenged this view, showing that STN‐HFS might also increase the activity of globus pallidus internalis (GPi) neurons that are under strong excitatory drive of the STN. In addition, most results emanate from studies applying acute STN‐HFS, while parkinsonian patients receive chronic stimulation. Thus, the present study was designed to assess the effect of chronic (10 days) STN‐HFS in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated nonhuman primate. For this purpose, 2‐deoxyglucose (2‐DG) uptake, a measure of global synaptic activity, was assessed in the basal ganglia and the motor thalamus after chronic unilateral STN‐HFS. Cytochrome oxidase subunit 1 (COI) mRNA expression, a marker of efferent metabolic activity, was additionally assessed in the globus pallidus. Chronic STN‐HFS (i) reversed abnormally decreased 2‐DG uptake in the STN of parkinsonian nonhuman primates, (ii) reversed abnormally increased 2‐DG accumulation in the GPi while COI mRNA expression was increased, suggesting global activation of GPi neurons, and (iii) reversed abnormally increased 2‐DG uptake in the ventrolateral motor thalamus nucleus. The simultaneous decrease in 2‐DG uptake and increase in COI mRNA expression are difficult to reconcile with the current model of basal ganglia function and suggest that the mechanisms by which STN‐HFS exerts its clinical benefits are more complex than a simple reversal of abnormal activity in the STN and its targets.
Bibliografia:	ark:/67375/WNG-LMF59FML-3 ArticleID:EJN5406 istex:2BF784D44A564CCEA585B31B04559FF03A3E8AEF ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0953-816X 1460-9568
DOI:	10.1111/j.1460-9568.2007.05406.x